Genes and susceptible loci of Alzheimer’s disease

• Published in: Brain Research Bulletin 1999-01, Vol.48 (2), p.121-127
• Main Authors: Shastry, Barkur S, Giblin, Frank J
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Amino Acid Sequence; Amyloid; Animals; Autosomal dominant; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Humans; Medical sciences; Molecular Sequence Data; Neurology; Presenilins; Transgenic mice
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/S0361-9230(98)00156-7

Alzheimer’s disease (AD) is the most common and devastating neurodegenerative disease of the elderly. Many research findings on familial AD suggest that the mechanisms of the pathogenesis of the disorder is more complex although the overall neuropathology of all cases of AD is surprisingly very similar. Genetic studies on some families have shown that mutations in the genes encoding β-amyloid precursor protein and presenilins 1 and 2 are responsible for early-onset AD. In addition, apolipoprotein E gene allele E4 and the bleomycin hydrolase locus are shown to be genetic risk factors for late-onset AD in certain sporadic cases. Mitochondrial dysfunctions and age-related oxidative stress may also contribute to degenerative processes in AD. Although several studies support the amyloid cascade hypothesis as the mechanism of the disease, transgenic experiments and recent findings on a variant form of an AD family suggest that Aβ deposition may not be sufficient to cause AD. Identification in the future of other genetic, environmental, and age-related factors, may provide additional targets for therapies.