From: Maternal transmission of Alzheimer's disease: Prodromal metabolic phenotype and the search for genes
Gene | Chromosome | Transmission | AD form | Prevalence | Clinical characteristics | In vivoimaging findings |
---|---|---|---|---|---|---|
APP | 21 | Autosomal dominant | EOFAD | 10-15% of EOFAD | Age of onset <65 years Increased processing of APP to Aβ42 | Reduced CMRglc on FDG-PET in pre-symptomatic and symptomatic mutation carriers |
APP | 21 | Autosomal recessive | EOFAD | na | Age of onset <50 years Increased Aβ production | na |
PSEN1 | 14 | Autosomal dominant | EOFAD | 30-70% of EOFAD | Age of onset 40-50 years Increased processing of APP to Aβ42 Rapid progression Associated with seizures, myoclonus and language deficits | Reduced CMRglc on FDG-PET and striatal amyloid deposition on PIB PET in pre-symptomatic and symptomatic mutation carriers |
PSEN2 | 1 | Autosomal dominant | EOFAD | <5% of EOFAD | Age of onset 40-70 years Increased Aβ42 production | na |
ApoE | 19 | 3 allelic variants: ε2, ε3, ε4 | LOAD | 40% of LOAD, 10-20% of controls | ApoE ε4 carriers vs non-carriers show lower age at onset, reduced Aβ clearance, poorer cognitive performance in late life | Hippocampal atrophy on MRI and reduced CMRglc on FDG-PET in pre-symptomatic and symptomatic ApoE ε4 carriers vs non-carriers |
SORL1 | 11 | SNPs: 8-10 and 22-25 gene regions | LOAD | 20-40% of LOAD | Increased Aβ production | Hippocampal atrophy on MRI in SORL1 carriers vs non-carriers |
KIBRA | 5 | SNP: T → C | LOAD | 45% of LOAD | Poorer episodic memory in CC carriers vs TT and TC carriers | Increased hippocampal activation on fMRI, and reduced CMRglc on FDG-PET in CC carriers vs CT and TT carriers |
GAB2 | 11 | 6 SNPs | LOAD | 70% of LOAD | CT-AAG- CAGATCAGACG vs TC-GCA- TGAGGTGTCTT haplotype: Less protection from neuronal tangle formation and cell death Increased risk of AD | na |
PCDH11X | X | SNP: Rs5984894 | LOAD | na | Increased risk of AD | na |