Research Interests:
We conducted a genome-wide association study in a cohort of 176 Italian Alzheimer’s disease (AD) patients with extreme phenotype of response to cholinesterase inhibitors. Patients were classified into responders in case of positive,... more
We conducted a genome-wide association study in a cohort of 176 Italian Alzheimer’s disease (AD) patients
with extreme phenotype of response to cholinesterase inhibitors. Patients were classified into responders
in case of positive, stable, or1 worsening of mini-mental state examination score and into nonresponders
if>3 points worsening during a median follow-up of 0.85 years of treatment. Forty-eight single-nucleotide
polymorphisms were selected for replication in 198 additional AD-treated patients. By using the dichotomous
response trait and a quantitative trait approach (change of mini-mental state examination),
a nominal replication and evidence of association when combining data were achieved for 2 singlenucleotide
polymorphisms associated with response to treatment: rs6720975A (pcombined ¼ 2.9 105,
beta regression coefficient: 1.61) and rs17798800A (pcombined ¼ 6.8 106, odds ratio ¼ 0.38, 95% confidence
interval ¼ 0.25e0.58). Rs6720975 maps in the intronic region of PRKCE, a protein kinase involved in
several cellular functions, whereas rs17798800 is intergenic and, according to expression quantitative trait
locus (eQTL) analysis, it acts as a cis-regulator of NBEA, an A kinaseeanchoring protein playing a substantial
role in the maturation of the nervous system. Despite its limitations, this project paves the way for the
application of personalized medicine in AD patients and for collaborative efforts in this field.
with extreme phenotype of response to cholinesterase inhibitors. Patients were classified into responders
in case of positive, stable, or1 worsening of mini-mental state examination score and into nonresponders
if>3 points worsening during a median follow-up of 0.85 years of treatment. Forty-eight single-nucleotide
polymorphisms were selected for replication in 198 additional AD-treated patients. By using the dichotomous
response trait and a quantitative trait approach (change of mini-mental state examination),
a nominal replication and evidence of association when combining data were achieved for 2 singlenucleotide
polymorphisms associated with response to treatment: rs6720975A (pcombined ¼ 2.9 105,
beta regression coefficient: 1.61) and rs17798800A (pcombined ¼ 6.8 106, odds ratio ¼ 0.38, 95% confidence
interval ¼ 0.25e0.58). Rs6720975 maps in the intronic region of PRKCE, a protein kinase involved in
several cellular functions, whereas rs17798800 is intergenic and, according to expression quantitative trait
locus (eQTL) analysis, it acts as a cis-regulator of NBEA, an A kinaseeanchoring protein playing a substantial
role in the maturation of the nervous system. Despite its limitations, this project paves the way for the
application of personalized medicine in AD patients and for collaborative efforts in this field.
Research Interests:
Magnetic Resonance Imaging, Mild Cognitive Impairment, Positron Emission Tomography, Hippocampus, Humans, and 16 moreGlucose, Cerebral Cortex, Female, Male, Clinical Sciences, Aged, Middle Aged, Atrophy, Biological markers, Sensitivity and Specificity, Memory Disorders, Alzheimer Disease, Neurosciences, Predictive value of tests, Cognition disorders, and Cohort Studies
Research Interests:
In the last decade familial frontotemporal dementia (FFTD) has emerged as a distinct clinical disease entity characterized by clinical and genetic heterogeneity. Here, we provide an extensive clinical and genetic characterization of two... more
In the last decade familial frontotemporal dementia (FFTD) has emerged as a distinct clinical disease entity characterized by clinical and genetic heterogeneity. Here, we provide an extensive clinical and genetic characterization of two Italian pedigrees presenting with FFTD (FAM047: 5 patients, 5 unaffected; FAM071: 4 patients, 11 unaffected). Genetic analysis showed a conclusive linkage (LOD score for D17S791/D17S951: 4.173) to chromosome 17 and defined a candidate region containing MAPT and PGRN genes. Recombination analysis assigned two different disease haplotypes to FAM047 and FAM071. In affected subjects belonging to both families, we identified a novel 4 bp deletion mutation in exon 7 of PGRN gene (Leu271LeufsX10) associated with a variable clinical presentation ranging from FTDP-17 to corticobasal syndrome. The age-related penetrance was gender dependent. Both mutations in MAPT and PGRN genes are associated with highly variable clinical phenotypes. Despite the profound diff...
Research Interests:
Genetics, Dementia, Neurobiology, Italy, Humans, and 14 moreMutation, Female, Male, Genetic linkage analysis, Clinical Sciences, Aged, Family Health, Single Photon Emission Computed Tomography, Frontotemporal Dementia, Genetic Analysis, Neurobiology of Aging, Clinical Presentation, Neurosciences, and Linkage Analysis
Deposits of tau and alpha-synuclein are hallmarks of distinct neurodegenerative diseases: tauopathies and alpha-synucleinopathies. Affinity chromatography experiments demonstrated a direct binding of the two proteins, and alpha-synuclein... more
Deposits of tau and alpha-synuclein are hallmarks of distinct neurodegenerative diseases: tauopathies and alpha-synucleinopathies. Affinity chromatography experiments demonstrated a direct binding of the two proteins, and alpha-synuclein was shown to induce fibrillization of tau. Here, we verify the presence of this physical interaction by using different cellular systems. This binding was abolished by the most common tau mutation (P301L) associated with frontotemporal dementia. We restored the impaired interaction by inducing heat shock proteins 70 and 90. In addition, we show that P301L tau mutation strongly affects tau and alpha-synuclein neuronal distribution.
Research Interests:
Confocal Microscopy, Protein-Protein Interaction, Cell line, Humans, Mutation, and 14 moreNeurons, Affinity chromatography, Physical Interaction, Clinical Sciences, Frontotemporal Dementia, Neurodegenerative Disease, Heat Shock, Transfection, Glutathione Transferase, Heat Shock Protein, Protein Binding, Parkinson Disease, Biochemistry and cell biology, and Cellular system
Research Interests:
Alzheimer’s disease (AD) is the major cause of dementia in the elderly. The biochemical changes that precede AD may be present up to 20 years before the clinical manifestation of the disease. The translational development of AD biomarkers... more
Alzheimer’s disease (AD) is the major cause of dementia in the elderly. The biochemical changes that precede AD may be present up to 20 years before the clinical manifestation of the disease. The translational development of AD biomarkers may be theoretically achieved via two different strategies: the first strategy can be defined as ‘knowledge-based’ (deductive method), while the second one
Research Interests:
Cognitive Science, Translational Research, Neurodegenerative Diseases, Cerebrospinal Fluid, Humans, and 12 moreAnimals, Knowledge Bases, Clinical Sciences, Knowledge base, microRNAs, Molecular Marker, Biological markers, Hypothesis Generation, Proteome, Alzheimer Disease, Neurosciences, and Translational Medical Research
CST3 is the coding gene for cystatin C (CysC). CST3 B/B homozygosity is associated with an increased risk of developing Alzheimer disease. We performed CysC analysis on human primary skin fibroblasts obtained from donors carrying A/A,... more
CST3 is the coding gene for cystatin C (CysC). CST3 B/B homozygosity is associated with an increased risk of developing Alzheimer disease. We performed CysC analysis on human primary skin fibroblasts obtained from donors carrying A/A, A/B, and B/B CST3. Pulse-chase experiments demonstrated that the release of the B variant of CysC has a different temporal pattern compared to that of the A one. Fibroblasts B/B homozygous displayed a reduced secretion of CysC due to a less efficient cleavage of the signal peptide, as suggested by high-resolution Western blot analysis and by in vitro assay. In the brain, the reduced level of CysC may represent the molecular factor responsible for the increased risk of Alzheimer disease.
Research Interests:
Research Interests:
Research Interests:
Magnetic Resonance Imaging, Humans, Cerebral Cortex, Female, Neuroimage, and 15 moreMale, Parietal Cortex, Pattern Matching, Apolipoprotein E, Neurons, Temporal Cortex, Aged, High Resolution, Atrophy, Medial Temporal Lobe, Permutation Test, Alzheimer Disease, Gray Matter, Clinical evaluation, and Neuropsychological Tests
This paper addresses a tenet of the literature on APOE, i.e., the relationship between the effects of the ε4, one of the established genetic risk factor for... more
This paper addresses a tenet of the literature on APOE, i.e., the relationship between the effects of the ε4, one of the established genetic risk factor for Alzheimer's disease (AD), and its expression levels as determined by APOE promoter polymorphisms. Five polymorphisms (-491 rs449647, -427 rs769446, -219 rs405509, and ε rs429358-rs7412) were studied in 1308 AD patients and 1082 control individuals from the Central-Northern Italy. Major findings of the present study are the following: 1) the variants -219T and ε4 increase the risk for late onset AD (LOAD) when they are both present in cis on the same chromosome (in phase); 2) the correlation between the haplotype (-219T/ε4) and AD risk persists when the data are stratified by age; 3) this haplotype likely anticipates the age of onset of the disease. These data, while confirming the association between -219T and AD, highlight the importance of the phase of the alleles for the observed effects on AD risk, suggesting that this information has to be taken into account when assessing the AD genetic risk. Moreover, the data help to clarify the apparent discrepancy that emerges from the genetic analysis where an SNP characterizing the haplotype responsible for an increased risk for LOAD is coherently associated with a reduced expression of ApoE levels. Our data are compatible with the hypothesis of a complex role of ApoE in the AD pathogenesis, with positive and negative effects occurring concomitantly according to its expression levels and its protein-protein interactions largely unclarified.
Research Interests:
Genetics, Cognitive Science, Polymorphism, Transgenic Mice, Italy, and 16 moreHumans, Haplotypes, Female, Male, Apolipoprotein E, Risk factors, Protein Interactions, Clinical Sciences, Longitudinal Studies, Genotype, Linkage Disequilibrium, Age Factors, Chi Square Distribution, Risk Factors, Alzheimer Disease, and Neurosciences
Expansion of a hexanucleotide repeat in the C9ORF72 gene has been identified as the most common pathogenic mutation in families with autosomal dominant frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis. Herein we... more
Expansion of a hexanucleotide repeat in the C9ORF72 gene has been identified as the most common pathogenic mutation in families with autosomal dominant frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis. Herein we investigated frequency and penetrance of the C9ORF72 hexanucleotide repeat pathological expansion in a large cohort of familial and sporadic FTLD and related disorders (FTLD and related disorders, n = 388; Controls, n = 201). Moreover, we weighed the impact of C9ORF72 genotype on clinical phenotype taking into account the hexanucleotide repeat units number as a possible disease modifier. In our cohort, the C9ORF72 pathological expansion: (i) showed a prevalence of 7.5%; (ii) showed a full penetrance by the age of 80; (iii) was rarely found in sporadic patients; (iv) was solely associated with FTLD; (v) was mainly associated with bvFTD clinical subtype; and (vi) was associated with earlier age of onset in the youngest generation compared with the previous generation within a pedigree. Interestingly, intermediate C9ORF72 expansion had a risk effect in familial/sporadic FTLD. Eventually, the C9ORF72 repeat units number influenced the disease phenotype in terms of age of onset and associated clinical subtype. Genome-wide studies in well characterized clinical cohorts will be essential in order to decipher pathways of disease expression in C9ORF72-associated neurodegeneration.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Polymorphism, Multidisciplinary, Logistic Regression, Phylogeny, Mitochondrial DNA, and 17 moreHumans, Mutation, Haplotypes, Female, Mitochondrial Respiratory Chain, Risk factors, PLoS one, Mitochondrial Genome, Cognitive Assessment, Aged, High Resolution, Oxidative phosphorylation, Neurodegenerative Disease, Risk Factors, Complex Traits, Alzheimer Disease, and Case Control Studies
Research Interests:
Decision Making, Dementia, Family, Risk assessment, Causality, and 17 moreItaly, Motivation, Genetic counseling, Cross-Cultural Comparison, Humans, Genetic Testing, genetic Counselling, United States, Female, Male, Attitudes, Pedigree, Middle Aged, Questionnaires, Adult, Risk Assessment, and Logistic Models
Research Interests:
Neuroscience, Psychology, Cognitive Science, Neuroimaging, Dementia, and 23 morePolymorphism, Magnetic Resonance Imaging, Morphometry, Postmenopausal Women, Brain, Humans, Genetic Testing, Cerebral Cortex, Female, Voxel Based Morphometry, Cytoprotection, Middle Aged, Atrophy, Estrogens, Genotype, Disease Progression, Cognitive Decline, Alzheimer Disease, Neurosciences, Gray Matter, Cognition disorders, Estrogen receptor alpha, and Magnetic resonance image
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Genetics, Neuroscience, Psychology, Cognitive Science, Polymorphism, and 18 moreHumans, Female, Male, Statistical Significance, Risk factors, Protein Function, Aged, Risk Factor, Kinesin, Genotype, Single Nucleotide Polymorphism, Frontotemporal Dementia, Risk Factors, In Silico, Neurosciences, Semantic Dementia, Linkage Analysis, and Case Control Studies
Research Interests:
Psychopharmacology, Depression, Schizophrenia, Diabetes, Cell Cycle, and 32 moreNeuropsychopharmacology, Apoptosis, Gene expression, Neuronal cell death, Cell Division, Cell line, Humans, Toxicity, Cerebral Cortex, Mice, Female, Animals, Cell Death, Immune regulation, Neurons, Trail, Neuroblastoma, T lymphocytes, Apoptose, Aged, Western blot, Tumor necrosis factor-alpha, Type 2 Diabetes Mellitus, Cell Cycle Proteins, Tumor Necrosis Factor–α (TNF), Ligand, Alzheimer Disease, Cell Survival, Ligands, islets of Langerhans, Gene Expression Regulation, and Pancreatic islets
Mutations in the progranulin gene (PGRN) were identified as the causal mechanism underlying frontotemporal lobar degeneration (FTLD). Most of these mutations are predicted to create null alleles leading to a 50% loss of progranulin... more
Mutations in the progranulin gene (PGRN) were identified as the causal mechanism underlying frontotemporal lobar degeneration (FTLD). Most of these mutations are predicted to create null alleles leading to a 50% loss of progranulin transcript. Patients underwent clinical and neurologic examination at the Memory Clinic of the IRCCS S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy. We enrolled affected (n = 6) and unaffected at risk members (n = 73) of families carrying the FTLD associated progranulin Leu271LeufsX10 mutation; additionally, we included subjects affected by sporadic/familial FTLD (n = 65), controls (n = 75), and a family carrying the tau P301L mutation. The presence of mutations in PGRN and MAPT genes was investigated by direct sequencing of exonic and flanking intronic regions. Progranulin plasma and CSF levels were measured using ELISA. We demonstrated that progranulin protein is strongly reduced (up to 3.93-fold) both in plasma and CSF of affected and unaffected subjects carrying mutations in progranulin gene (PGRN Leu271LeufsX10 and Q341X). We established a plasma progranulin protein cutoff level of 74.4 ng/mL that identifies, with specificity and sensitivity of 100%, mutation carriers among unaffected subjects. In FTLD, values <or=110.9 ng/mL give a specificity of 92.8% and a sensitivity of 100% for PGRN mutations. We propose the dosage of plasma progranulin as a useful tool for a quick and inexpensive large-scale screening of carriers of progranulin mutations and for monitoring future treatments that might boost the level of this protein.
Research Interests:
Cognitive Science, Neurology, Dementia, Humans, Mutation, and 7 moreMale, Pedigree, Clinical Sciences, Aged, Middle Aged, Adult, and Neurosciences
Research Interests:
Genetics, Magnetic Resonance Imaging, Aging, Mild Cognitive Impairment, Electroencephalography, and 19 moreNeuroimmunology, Humans, Female, Neuroimage, Male, Statistical Significance, Apolipoprotein E, Risk factors, Aged, Middle Aged, Genotype, Adult, cystatin C, Risk Factors, Genetic Association, Alzheimer Disease, Low Resolution, Cognition disorders, and Neuropsychological Tests
Recently, attention was drawn to a role for progranulin in the central nervous system with the identification of mutations in the progranulin gene (GRN) as an important cause of frontotemporal lobar degeneration. GRN mutations are... more
Recently, attention was drawn to a role for progranulin in the central nervous system with the identification of mutations in the progranulin gene (GRN) as an important cause of frontotemporal lobar degeneration. GRN mutations are associated with a strong reduction of circulating progranulin and widely variable clinical phenotypes: thus, the dosage of plasma progranulin is a useful tool for a quick and inexpensive large-scale screening of carriers of GRN mutations. To establish the best cutoff threshold for normal versus abnormal levels of plasma progranulin. 309 cognitively healthy controls (25-87 years of age), 72 affected and unaffected GRN+ null mutation carriers (24-86 years of age), 3 affected GRN missense mutation carriers, 342 patients with neurodegenerative diseases and 293 subjects with mild cognitive impairment were enrolled at the Memory Clinic, IRCCS S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy, and at the Alzheimer Unit, Ospedale Maggiore Policlinico and IRCCS Istituto Neurologico C. Besta, Milan, Italy. Plasma progranulin levels were measured using an ELISA kit (AdipoGen Inc., Seoul, Korea). Plasma progranulin did not correlate with age, gender or body mass index. We established a new plasma progranulin protein cutoff level of 61.55 ng/ml that identifies, with a specificity of 99.6% and a sensitivity of 95.8%, null mutation carriers among subjects attending to a memory clinic. Affected and unaffected GRN null mutation carriers did not differ in terms of circulating progranulin protein (p = 0.686). A significant disease anticipation was observed in GRN+ subjects with the lowest progranulin levels. We propose a new plasma progranulin protein cutoff level useful for clinical practice.
Research Interests:
Cognitive Science, Mild Cognitive Impairment, Translational Research, Neurodegenerative Diseases, Italy, and 17 moreClinical Practice, Humans, Mutation, Female, Male, Central Nervous System, Body Mass Index, Clinical Sciences, Aged, Middle Aged, Adult, Neurodegenerative Disease, Large Scale, Sensitivity and Specificity, Neurosciences, Predictive value of tests, and Age of Onset
Research Interests:
There is now considerable evidence that the gene encoding for tau protein (MAPT) is implicated in frontotemporal dementia (FTD). The role of MAPT haplotypes in neurodegenerative diseases has been suggested, but their contribution in... more
There is now considerable evidence that the gene encoding for tau protein (MAPT) is implicated in frontotemporal dementia (FTD). The role of MAPT haplotypes in neurodegenerative diseases has been suggested, but their contribution in familial dementia has not been extensively investigated. Here, we investigated (1) the association between the MAPT haplotypes and sporadic (sFTD) or familial FTD (FFTD) (controls n = 99, sFTD n = 53, FFTD n = 50), (2) the interactive effect between MAPT haplotypes and APOE gene. We found an overrepresentation of H2 haplotype (OR = 1.83, P = 0.029) and of H2H2 genotype in FFTD patients (OR = 6.09, P = 0.007). This association was even stronger in APOE e4 negatives FFTD (H2: OR = 2.9, P = 0.001; H2H2: OR = 12.67, P = 0.001). Our results support idea that the MAPT H2 haplotype is a risk factor for FFTD. This locus could contain this or other inheritable genetic determinants contributing to increase risk of developing dementia.
Research Interests:
Genetics, Neurobiology Of Disease, Dementia, Neurobiology, Humans, and 18 moreGenetic Testing, Mutation, Cerebral Cortex, Haplotypes, Female, Male, Apoe, Apolipoprotein E, Risk factors, Clinical Sciences, Aged, Middle Aged, Genotype, Frontotemporal Dementia, Neurodegenerative Disease, Interaction effect, Risk Factors, and Neurosciences
Research Interests:
Immunohistochemistry, Confocal Microscopy, Stem Cell, Neurobiology, Humans, and 19 moreMutation, Cerebral Cortex, Mice, Protein Secretion, Animals, Threonine, Neurons, Clinical Sciences, Methionine, cystatin C, Presenilin-2, Tubulin, Arginine, Transfection, Neurobiology of Aging, Alzheimer Disease, Cell Survival, Neurosciences, and Protein Transport
Research Interests:
Genetics, Dementia, Neurobiology, Italy, Humans, and 14 moreMutation, Female, Male, Genetic linkage analysis, Clinical Sciences, Aged, Family Health, Single Photon Emission Computed Tomography, Frontotemporal Dementia, Genetic Analysis, Neurobiology of Aging, Clinical Presentation, Neurosciences, and Linkage Analysis
Research Interests:
Research Interests:
Research Interests:
Estrogens are known to be protective in age-associated cognitive changes in humans and in neurodegeneration in animal models. The aim of this study was to evaluate the potential effects of estrogen therapy (ET) on human gray matter volume... more
Estrogens are known to be protective in age-associated cognitive changes in humans and in neurodegeneration in animal models. The aim of this study was to evaluate the potential effects of estrogen therapy (ET) on human gray matter volume in vivo. Forty healthy postmenopausal women underwent three-dimensional high-resolution magnetic resonance imaging: 17 were never treated, 16 were currently receiving ET, and 7 had had ET in the past. Voxel-based morphometry (VBM) with SPM2 was used, according to an optimized protocol, to compare women under past and current ET to those never treated. Significance threshold was set at P = 0.01, corrected by false discovery rate. Voxel-based morphometry indicated that estrogen use was associated with greater gray matter volumes in the whole group of treated women, which included the cerebellum (cluster size, Z coordinates: 5,527; 5.15; -14 -54 -10), the amygdaloid-hippocampal complex (left: 19; 3.55; -22 -4 -18; right: 45; 3.61; 16 -6 -16), and extended to the frontal, temporal, parietal, and occipital neocortex. The comparison current ET versus past ET use showed that women who underwent treatment in the past had greater volumes of gray matter compared to women under current treatment. ET might slow down age-related gray matter loss in postmenopausal women. The structures that exhibited greater volume in association with ET included the cerebellar and cerebral cortices and, typically involved in Alzheimer's disease, the medial temporal structures and the temporoparietal junction.
Research Interests:
Research Interests:
Research Interests:
Neurology, Dementia, Humans, Genetic Testing, Female, and 14 moreMale, Risk factors, Clinical Sciences, Aged, Genotype, Single Nucleotide Polymorphism, Linkage Disequilibrium, European Continental Ancestry Group, Risk Factors, Amino Acid Substitution Rates, Alzheimer Disease, Genetic Markers, Neurosciences, and Association Analysis
Research Interests:
Psychology, Membrane Proteins, Oxidative Stress, Mitochondria, Transcription Factors, and 13 moreGene expression, Energy Metabolism, Antioxidants, Brain, Humans, Transcription Factor, Mitochondrial dysfunction, Presenilin-2, Alzheimer Disease, Neurosciences, Oxidation-Reduction, Gene Expression Regulation, and Down-Regulation
Research Interests:
Psychology, Mild Cognitive Impairment, Humans, Blood Glucose, Hypertension, and 25 moreInsulin, Blood Pressure, Cholesterol, Female, Male, Regression Analysis, Potassium, Triglycerides, Clinical Sciences, Aged, Middle Aged, Adult, Sodium, Neural, Receptor for Advanced Glycation End Products, Cognitive Decline, Cross Sectional Studies, Alzheimer Disease, Neurosciences, Enzyme Linked Immunosorbent Assay, Creatinine, Age of Onset, Cognition disorders, Case Control Studies, and Statistics as Topic
Research Interests:
Psychology, Environmental Pollution, Manganese, Italy, Heavy metals, and 21 moreHumans, Liver, Copper, Female, Male, Transferrin, Disease Severity, Zinc, Iron, Liver Function, Bilirubin, Rating Scale, Aged, Middle Aged, Time Factors, Neural, Neurosciences, Aspartate Aminotransferases, Environmental Exposure, Alanine Transaminase, and Severity of Illness Index
To investigate the possible effect of the APOE epsilon4 allele on age-related regional volume loss within the corpus callosum (CC) in healthy epsilon4 allele carriers compared with noncarriers. A total of 211 subjects, ages 27 to 83... more
To investigate the possible effect of the APOE epsilon4 allele on age-related regional volume loss within the corpus callosum (CC) in healthy epsilon4 allele carriers compared with noncarriers. A total of 211 subjects, ages 27 to 83 years, 51 epsilon4 carriers and 160 noncarriers underwent T1-weighted MRI scan. All subjects had normal MRI scan and performed within normal range on a neuropsychological battery of tests. CC was segmented into seven functionally relevant regions using a previously published probabilistic map of the CC connectivity. We measured the volumes of the CC and its subregions. We used a regression model (with volumes as dependent and age as independent variables) and compared the slopes between carriers and noncarriers using an analysis of covariance model. We also carried out voxel-based-morphometry analysis to investigate the possible effect of the APOE epsilon4 gene on the gray matter. We found that the volume of the CC and all subregions decreased with increasing age in both groups. The slope was steeper in the APOE epsilon4 carriers compared withthe noncarriers particularly in the prefrontal region (P = 0.02). No gray matter differences were observed between the two groups. APOE epsilon4 polymorphism is associated with accelerated age-related volume loss in the prefrontal callosal tracts without gray matter loss. This result suggests the role of APOE epsilon4 in the brain aging by primarily affecting white matter structures particularly in the frontal lobe.
Research Interests:
Research Interests:
Polymorphism, Mild Cognitive Impairment, Brain, Humans, Blood Pressure, and 13 moreCerebrovascular Disease, Female, Male, Magnetic Resonance, Risk factors, Clinical Sciences, Aged, cystatin C, Risk Factors, Confidence Interval, Cognition disorders, White Matter Lesions, and Severity of Illness Index
Research Interests:
Psychology, Stem Cells, Stem Cell, Gene expression, Down Syndrome, and 21 moreWestern blotting, Neural stem cell, Brain, Complication, Humans, Skin, Neurons, Clinical Sciences, mRna expression levels, Adult, Sjogren´s Syndrome, Western blot, Protein Expression, Experimental Neurology, Molecular weight, Human Fibroblasts, Brain Chemistry, Reference Values, Alzheimer Disease, Neurosciences, and Control Group
Research Interests:
Research Interests:
The microtubule-associated protein Tau (MAPT) gene codes for the protein Tau that is involved in the pathogenesis of neurodegenerative diseases. Recent studies have detected an over-representation of the H1 haplotype of the MAPT gene in... more
The microtubule-associated protein Tau (MAPT) gene codes for the protein Tau that is involved in the pathogenesis of neurodegenerative diseases. Recent studies have detected an over-representation of the H1 haplotype of the MAPT gene in neurodegenerative disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia (FTD) and Parkinson's disease (PD), whereas the H2 haplotype has been found to be related to familial FTD. We aimed to investigate the association between MAPT haplotype status and brain morphology in healthy adults. A total of 150 healthy subjects underwent 3D high-resolution magnetic resonance (MR). MR images were processed following an optimized protocol to perform the Voxel-based morphometry (VBM) comparisons of the gray matter (GM) in H1 carriers (n=141) in contrast to H2H2 homozygous (n=9), and H1H1 homozygous (n=85) in contrast to H2 carriers (n=65). The threshold for statistical significance was 0.005 uncorrected. Opposite comparisons were also carried out. The groups had similar demographic and cognitive features. Compared with H2H2, the H1 carriers showed up to 19% smaller GM volume in the head of the right caudate nucleus, in the right middle frontal gyrus, in the left insula and orbito-frontal cortex, and in the inferior temporal and inferior cerebellar lobes, bilaterally. Compared with all H2 carriers, H1H1 displayed lower GM in the same regions, but the effect was smaller (5%), possibly due to a dilution effect by H1 in the H2 carriers group. The data suggest that H1 haplotype is associated with a particular cerebral morphology that may increase the susceptibility of the healthy carriers to develop neurodegenerative diseases such as sporadic tauopathies.