Relationship between genetic risk factors and markers for Alzheimer's disease pathology

Lyzel S Elias-Sonnenschein; Lars Bertram; Pieter Jelle Visser

doi:10.2217/bmm.12.56

Relationship between genetic risk factors and markers for Alzheimer's disease pathology

Biomark Med. 2012 Aug;6(4):477-95. doi: 10.2217/bmm.12.56.

Authors

Lyzel S Elias-Sonnenschein¹, Lars Bertram, Pieter Jelle Visser

Affiliation

¹ School for Mental Health & Neuroscience, Alzheimer Centrum Limburg, Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, The Netherlands. lyzel.elias@maastrichtuniversity.nl

PMID: 22917148
DOI: 10.2217/bmm.12.56

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuritic plaques (main constituent: β-amyloid [Aβ]) and neurofibrillary tangles (hyperphosphorylated tau protein) in the brain. Abnormalities in Aβ and tau can be measured upon neuropathological examination, in cerebrospinal fluid or by PET. Etiologically, a growing body of evidence suggests that susceptibility to AD is genetically controlled. However, the precise nature of the underlying risk genes and their relation to AD biomarkers remains largely elusive. To this end, we performed a qualitative review of 17 studies (covering 47 polymorphisms in 26 genes) and investigated the potential relation between the most compelling AD risk genes and markers for Aβ and tau in cerebrospinal fluid, PET imaging and neuropathological examination. Of all covered genes, only APOE and PICALM showed consistent effects on Aβ but not on tau, while no obvious effects were observed for CLU, CR1, ACE, SORL and MAPT.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Alzheimer Disease / genetics*
Alzheimer Disease / metabolism
Alzheimer Disease / pathology
Apolipoproteins E / genetics
Apolipoproteins E / metabolism
Clusterin / genetics
Clusterin / metabolism
Genome-Wide Association Study
Humans
Monomeric Clathrin Assembly Proteins / genetics
Monomeric Clathrin Assembly Proteins / metabolism
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Polymorphism, Genetic
Receptors, Complement 3b / genetics
Receptors, Complement 3b / metabolism
Risk Factors
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism

Substances

Adaptor Proteins, Signal Transducing
Apolipoproteins E
BIN1 protein, human
CLU protein, human
CR1 protein, human
Clusterin
Monomeric Clathrin Assembly Proteins
Nuclear Proteins
PICALM protein, human
Receptors, Complement 3b
Tumor Suppressor Proteins