title: Molecular Basis of Familial and Sporadic Alzheimer's Disease.
abstract: Alzheimer's disease (AD) is a multifactorial disease with genetic (70%) and environmental (30%) causes. Among the genetic factors are genes associated with a family history of the disease (familial AD, FAD) and sporadic AD (SAD). The genes: APP (amyloid precursor protein), PSEN1 (Presenilin 1) and PSEN2 (Presenilin 2) are responsible for the presence of FAD. The APOE gene is responsible for the sporadic form of the disease. Other molecular factors related to the immunological cause (TREM2) of the disease are a disorder of the lipid (ABCA1, ABCA7) or biothiol (MTHFD1) metabolism and of the transport of metabolites (BIN1). Currently, it is believed that APOE is a risk factor for both SAD and late-onset FAD. The pathomechanism of AD is most commonly explained as based on the amyloid cascade theory. This theory is related to the FAD, although there are reports indicating the probability of its occurrence in the SAD. It seems that the excessive deposition of β-amyloid (Aβ) peptides and intracellular neurofibrillary tangles of tau protein hyperphosphorylated forms contribute to the damage of both DNA and RNA. Furthermore, it is believed that RNA-interference can affect both the level of pathological proteins (Aβ, tau protein) and the onset and progress of AD. It seems that a complete understanding of both FAD and SAD pathogenesis may contribute to the search for earlier clinical diagnosis and to an understanding of later occurrence of the disease, which may help modify its course and affect more effective therapy of this incurable neurological disease.
authors.affiliation: Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, 49, Przybyszewskiego St., 60-355 Poznan, Poland. dorszewskaj@yahoo.com.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Dorszewska
authors.forename: Michal
authors.initials: M
authors.lastname: Prendecki
authors.forename: Anna
authors.initials: A
authors.lastname: Oczkowska
authors.forename: Mateusz
authors.initials: M
authors.lastname: Dezor
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kozubski
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D006801:Humans