Molecular Neurobiology of Alzheimer's Disease.
- Author:
Young Hoon KIM
1
;
Chung Goo RHEE
;
Yong Kwan KIM
;
Sung Soo KIM
Author Information
1. Department of Psychiatry, College of Medicine, Inje University, Pusan, Korea.
- Publication Type:Original Article
- Keywords:
Alzheimer's disease;
Neurobilogy;
beta-Amyloid protein;
Pesenilin amyloid precursor protein;
tau protein
- MeSH:
Age of Onset;
Aged;
Alleles;
Alzheimer Disease*;
Amyloid;
Amyloid beta-Peptides;
Apolipoproteins;
Apolipoproteins E;
Autopsy;
Biology;
Cerebral Cortex;
Chromosomes, Human, Pair 1;
Chromosomes, Human, Pair 14;
Chromosomes, Human, Pair 19;
Chromosomes, Human, Pair 21;
Dementia;
Diagnosis;
Hippocampus;
Humans;
Neurobiology*;
Neurofibrillary Tangles;
Plaque, Amyloid;
Presenilins;
tau Proteins;
Wills
- From:Journal of Korean Geriatric Psychiatry
1998;2(1):37-46
- CountryRepublic of Korea
- Language:Korean
-
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.
