Alzheimer's disease

Alzheimer's disease (AD), a neurodegenerative disorder, is the most common cause of dementia and characterised clinically by progressive intellectual deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. The most striking early symptom is memory loss (amnesia), usually manifest as minor forgetfulness that becomes steadily more dense with illness progression, with relative preservation of older memories. As the disorder progresses, cognitive (intellectual) impairment extends to the domains of language (aphasia), coordinated movement (apraxia), recognition (agnosia) and those functions (such as decision-making and planning) closely related to the frontal lobe of the brain, reflecting extension of the underlying pathological process. This consists principally of neuronal (cell) loss (or atrophy), together with deposition of amyloid plaques and neurofibrillary tangles. Genetic factors are known to be important, and polymorphisms (variations) in three different autosomal dominant genes - Presenilin 1, Presenilin 2, and A-Beta - have been identified that account for a small number of cases of familial, early-onset AD. For late onset AD (LOAD), only one susceptibility gene has so far been identitified - the epsilon 4 allele of the APOE gene. Age of onset itself has a heritability of around 40%.

Genetic and population effects

Various gene alleles have been associated with Alzheimer's disease, most notably the apolipoprotein E (ApoE) gene. ApoE normally functions to regulate cholesterol metabolism. In addition, it has recently been discovered that Chinese and North American populations differ significantly in development of full-fledged Alzheimer's from early warning symptoms. Whether the reason for this is genetic, dietary, or social has yet to be investigated.

Related Topics:
Allele - Cholesterol - Metabolism

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The ApoE4 form of ApoE, which is associated with Alzheimer's, is found at the highest rates among long-time hunter-gatherers, and at the lowest rates among populations who have been accustomed to agriculture the longest. This has led some researchers to suggest that ApoE4, which exerts some of the same effects on metabolism as a diet excessively high in carbohydrates, contributes to Alzheimer's only in conjunction with an evolutionary discordant high-carbohydrate diet. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15716586&query_hl=8

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