J Korean Geriatr Psychiatry.  1998 May;2(1):37-46.

Molecular Neurobiology of Alzheimer's Disease

Affiliations
  • 1Department of Psychiatry, College of Medicine, Inje University, Pusan, Korea.
  • 2Institute of Neuroscience, Inje University, Pusan, Korea.

Abstract

Alzheimer's disease (AD), the most common dementia in the elderly, is associated with a characteristic neuropathology:extracellular neuritic plaques (NPs) and intraneuronal neurofibrillary tangles (NFTs). AD is diagnosed clinically on the basis of progressive cognitive impairment. However, the diagnosis of AD is only reliable if a histopathological examination at autopsy shows high numbers of NPs and NFTs particularly in the hippocampus and cerebral cortex. The major component of NP is beta-amyloid protein (Abeta), a fragment of the amyloid precursor protein (APP). NFTs are largely composed of paired helical filaments (PHFs) containing abnormally phospholylated form of the microtubule-associated protein (MAP), tau. A genetic etiology for AD has been established based on population survey. It is revealed that 25-40% of the AD patients are familial and the disease is inherited as an autosomal-dominant trait in most families. Age at onset patterns of AD patients in affected families had indicated that its distribution is bimodal with a cut-off age 58 years. Several mutations in the APP gene, located on chromosome 21, are linked to early-onset AD (EOAD). However, these account for only a small fraction of cases of EOAD. The remaining cases are associated with mutations in two other genes:one on chromosome 14 that encodes S182 (presenilin 1) and the other on chromosome 1 that encodes STM2 (presenilin 2). It is also known that inheritance of specific apolipoprotein E (apoE) alleles, located on chromosome 19, determines the risk and mean age of onset of late-onset AD (LOAD). In this review, we will briefly discuss the biology and hypothetical mechanisms of Abeta, presenilins, apoE and tau protein, those involved in the pathogenesis of AD.

Keyword

Alzheimer's disease; Neurobilogy; beta-Amyloid protein; Pesenilin amyloid precursor protein; tau protein
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