Alzheimer's disease, beta-amyloidosis, and aging.
Alzheimer's disease (AD) is rapidly moving from the obscure category of degenerative diseases to the more precise one of metabolic disorders. Recent discoveries have substantiated the hypothesis that AD results from the deposition of beta-amyloid, which is formed by polymers of a proteolytic fragment of the amyloid protein precursor (APP), and may induce intraneuronal aggregation of the microtubule-associated protein tau into paired helical filaments and neuronal death. There is also evidence that AD is a heterogeneous age-related disorder of multifactorial origin, which may arise as a consequence of point mutations of genes encoding APP or other proteins involved in its metabolism (familial AD), or a combination of genetic and non-genetic factors (sporadic AD). Familial AD displays genetic and phenotypic heterogeneity, meaning that mutations of different genes may cause the AD phenotype, and that different mutations of the same gene may cause phenotypically distinct disorders, including Alzheimer-type dementia and cerebral amyloid angiopathy with cerebral hemorrhages and stroke. On the other hand, aging, gender, head trauma, and variants of the apolipoprotein E gene have been shown to increase the risk of developing the more prevalent sporadic form of AD. The mechanisms by which these factors influence amyloidogenesis are beginning to be understood, and this will provide a rational basis for future therapy. Knowledge of the molecular basis of AD would eventually allow accurate risk prediction before the disease becomes clinically apparent, and better chances for early treatment and prevention.
Coria
F
F
Section of Neurology, Complejo Hospitalario de Segovia, Spain.
Rubio
I
I
Bayón
C
C
D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data
D000682:Amyloid