The genetics and neuropathology of Alzheimer's disease.

TitleThe genetics and neuropathology of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2012
AuthorsSchellenberg GD, Montine TJ
JournalActa Neuropathol
Date Published2012 Sep
KeywordsAlzheimer Disease, Amyloid beta-Protein Precursor, Apolipoproteins E, Brain, Genetic Predisposition to Disease, Humans, Mutation, Polymorphism, Single Nucleotide, Presenilin-1, Presenilin-2

Here we review the genetic causes and risks for Alzheimer's disease (AD). Early work identified mutations in three genes that cause AD: APP, PSEN1 and PSEN2. Although mutations in these genes are rare causes of AD, their discovery had a major impact on our understanding of molecular mechanisms of AD. Early work also revealed the ε4 allele of the APOE as a strong risk factor for AD. Subsequently, SORL1 also was identified as an AD risk gene. More recently, advances in our knowledge of the human genome, made possible by technological advances and methods to analyze genomic data, permit systematic identification of genes that contribute to AD risk. This work, so far accomplished through single nucleotide polymorphism arrays, has revealed nine new genes implicated in AD risk (ABCA7, BIN1, CD33, CD2AP, CLU, CR1, EPHA1, MS4A4E/MS4A6A, and PICALM). We review the relationship between these mutations and genetic variants and the neuropathologic features of AD and related disorders. Together, these discoveries point toward a new era in neurodegenerative disease research that impacts not only AD but also related illnesses that produce cognitive and behavioral deficits.

Alternate JournalActa Neuropathol.
PubMed ID22618995
PubMed Central IDPMC3708460
Grant ListAG05136 / AG / NIA NIH HHS / United States
P50 AG005136 / AG / NIA NIH HHS / United States
RC2 AG036528 / AG / NIA NIH HHS / United States
RC2AG036528 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
U01AG032984 / AG / NIA NIH HHS / United States