Inheritance of Alzheimer's Disease: Epidemiologic Evidence

Abstract

The available evidence suggests that there may be two subtypes of AD – inherited and noninherited. Inherited AD may have certain characteristics, e.g. younger age at onset and some clinical signs or symptoms, which distinguish them from noninherited cases. It is possible that the noninherited type of AD may also have a similar genetic defect as the inherited kind, the only difference being that in one case the defect is inherited from the parents and in the other the defect arises de novo during embryogenesis. An environmental factor operating during embryogenesis may be responsible for causing a genetic defect which later manifests as noninherited AD. Currently, however, there is no precise way to separate these two subtypes. The exact proportion of all cases of AD which are inherited on a genetic basis is not known, but it must be small. The mode of inheritance of genetic AD is not known. It must be emphasized that the subtypes of inherited and noninherited AD are not synonymous with the older categorization of AD into presenile and senile AD.

Exome sequencing in an Italian family with Alzheimer’s disease points to a role for seizure-related gene 6 (SEZ6) rare variant R615H

“…Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder whose onset is mostly sporadic [ 1 ]. The genetic background has a major role in AD, and DNA variants may contribute, ranging from predisposing risk factors (having from medium to large effect size, such as the ε4 allele of the APOE gene) [ 2 ] to full penetrant causal mutations in a few genes, namely presenilins ( PSEN1 and PSEN2 ) and the amyloid-β (A4) precursor protein ( APP ) [ 3 , 4 ].…”

Is Dementia of the Alzheimer Type a Purely Genetic Illness? A Modelling Approach

“…There are indeed strong arguments in favor of the genetic origin of some DAT cases, but the distribution pattern of the disease in the population is not unequivocally genetic (fa milial) or environmental (sporadic), or, to be more precise, inherited or non-inherited [1], In certain families with multiple early-onset DAT cases, the familial pattern is very sug gestive of a genetic illness with an autosomal dominant mode of inheritance [2][3][4]. Fur thermore, in some of these families a genetic defect has been located on chromosome 21 by linkage studies [4,5], However, two restrictions should be made: Firstly, some studies have failed to confirm the linkage to chromosome 21 [6,7], and secondly, high-density families are scant and the majority of DAT cases are late-onset and sporadic [8].…”