We searched PubMed for English language articles on Alzheimer's disease using the keyword “Alzheimer” alone or together with other keywords including: “amyloid”, “CSF”, “CT”, “diagnosis”, “epidemiology”, “genetic”, “imaging”, “MRI”, “PET”, “risk factors”, “tau”, “therapy”, “transgenic”, “treatment”, and several other keywords relevant to every section. We largely selected publications in the past 5 years, but did not exclude important older publications. Selection criteria also included a
Seminar
Alzheimer's disease
Section snippets
Epidemiology and risk factors
Alzheimer's disease is the most common form of dementia, accounting for 50–60% of all cases. The prevalence of dementia is below 1% in individuals aged 60–64 years, but shows an almost exponential increase with age, so that in people aged 85 years or older the prevalence is between 24% and 33% in the Western world.2 Representative data from developing countries are sparse, but about 60% of patients with dementia are estimated to live in this part of the world. Alzheimer's disease is very common
Genetics
From a genetic standpoint, Alzheimer's disease is a heterogeneous disorder with both familial and sporadic forms.
Pathogenesis
At the microscopic level, the characteristic lesions in Alzheimer's disease are senile or neuritic plaques and neurofibrillary tangles (figure 1) in the medial temporal lobe structures and cortical areas of the brain, together with a degeneration of the neurons and synapses. Several pathogenic mechanisms that underlie these changes have been studied, including Aβ aggregation and deposition with plaque development, tau hyperphosphorylation with tangle formation, neurovascular dysfunction, and
Clinical features
Alzheimer's disease is a slowly progressive disorder, with insidious onset and progressive impairment of episodic memory; instrumental signs include aphasia, apraxia, and agnosia, together with general cognitive symptoms, such as impaired judgment, decision-making, and orientation.
The term Alzheimer's disease was originally reserved for individuals with presenile onset of symptoms, whereas the expression senile dementia was used when onset was after 65 years of age. Largely on the basis of
Diagnosis
The medical history together with the clinical, neurological, and psychiatric examination serves as the basis in the diagnostic work-up. In very early cases, neuropsychological testing can help to obtain objective signs of memory disturbances. Laboratory studies, such as thyroid-function tests and serum vitamin B12, are necessary to identify secondary causes of dementia and coexisting disorders that are common in elderly people.
Neuroimaging, CT and MRI, plays an important part in the diagnosis
Treatment
Knowledge of the neurotransmitter disturbances in Alzheimer's disease has led to the development of drugs with symptomatic effects, which are approved in many countries. Research advances in the molecular pathogenesis of Alzheimer's disease have also led to new drug candidates with disease-modifying potential, which have now come to testing in clinical trials. Epidemiological data have suggested additional drug candidates, some of which have been investigated in randomised trials.
Future prospects
The past two decades of Alzheimer's disease research have resulted in detailed knowledge of the molecular mechanism of Aβ production and aggregation. With the amyloid cascade hypothesis serving as the foundation, and the Alzheimer's disease transgenic mouse models as the tools for testing, anti-Aβ drug candidates have been developed. Several phase II clinical trials are now ongoing or under planning. The key question that will determine whether these will be successful is not only whether the
Search strategy and selection criteria
References (184)
- et al.
Global prevalence of dementia: a Delphi consensus study
Lancet
(2005) - et al.
Dietary factors and Alzheimer's disease
Lancet Neurol
(2004) - et al.
Apolipoprotein E polymorphism and Alzheimer's disease
Lancet
(1993) Apolipoprotein E in animal models of CNS injury and in Alzheimer's disease
Trends Neurosci
(1994)- et al.
ApoE genotype accounts for the vast majority of AD risk and AD pathology
Neurobiol Aging
(2004) - et al.
Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor
J Biol Chem
(1998) - et al.
Clearance of Alzheimer's Abeta peptide: the many roads to perdition
Neuron
(2004) - et al.
Deciphering the molecular basis of memory failure in Alzheimer's disease
Neuron
(2004) - et al.
Tau pathology in Alzheimer disease and other tauopathies
Biochim Biophys Acta
(2005) - et al.
Cerebral microvascular pathology in aging and Alzheimer's disease
Prog Neurobiol
(2001)
The cell cycle in Alzheimer disease: a unique target for neuropharmacology
Mech Ageing Dev
The potential of anti-inflammatory drugs for the treatment of Alzheimer's disease
Lancet Neurol
Oxidative stress in Alzheimer's disease
Neurobiol Aging
Are mitochondria critical in the pathogenesis of Alzheimer's disease?
Brain Res Brain Res Rev
Plaques, tangles and dementia. A quantitative study
J Neurol Sci
Normal ageing, impaired cognitive function, and senile dementia of the Alzheimer's type: a continuum?
Lancet
Mild cognitive impairment
Lancet
Abnormal cortisol response in Alzheimer's disease linked to hippocampal atrophy
Lancet
Positron emission tomography and magnetic resonance imaging in the diagnosis and prediction of dementia
Alzheimers Dementia
MRI-derived entorhinal volume is a good predictor of conversion from MCI to AD
Neurobiol Aging
Hippocampus and entorhinal cortex in mild cognitive impairment and early AD
Neurobiol Aging
Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET
Neuroimage
Hippocampal formation glucose metabolism and volume losses in MCI and AD
Neurobiol Aging
PET imaging of amyloid in Alzheimer's disease
Lancet Neurol
CSF markers for incipient Alzheimer's disease
Lancet Neurol
Cerebrospinal fluid protein biomarkers for Alzheimer's disease
Neuro Rx
Preclinical Alzheimer's disease: diagnosis and prediction of progression
Lancet Neurol
Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study
Lancet Neurol
The case described by Alois Alzheimer in 1911. Historical and conceptual perspectives based on the clinical record and neurohistological sections
Eur Arch Psychiatry Clin Neurosci
Epidemiology of neurodegeneration
Annu Rev Neurosci
Head circumference, education and risk of dementia: findings from the Nun Study
J Clin Exp Neuropsychol
Head injury and dementia
Curr Opin Neurol
Role of genes and environments for explaining Alzheimer disease
Arch Gen Psychiatry
Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease
Nature
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Nature
Candidate gene for the chromosome 1 familial Alzheimer's disease locus
Science
The prevalence and causes of dementia in people under the age of 65 years
J Neurol Neurosurg Psychiatry
Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Science
Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis
JAMA
ApoE genotype predicts when–not whether–one is predisposed to develop Alzheimer's disease
Nature Genetics
Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease
Proc Natl Acad Sci USA
APOE epsilon4 allele is associated with reduced cerebrospinal fluid levels of Abeta42
Neurology
Towards compendia of negative genetic association studies: an example for Alzheimer disease
Hum Genet
The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects
Br J Psychiatry
Amyloid plaque core protein in Alzheimer disease and Down syndrome
Proc Natl Acad Sci USA
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Nature
Amyloid beta-peptide is produced by cultured cells during normal metabolism
Nature
The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease
J Clin Invest
Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE
Science
Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease
Proc Natl Acad Sci USA
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