APOE polymorphism and clinical duration determine regional neuropathology in Swedish APP(670, 671) mutation carriers: implications for late-onset Alzheimer's disease.
Neurofibrillary changes throughout the brain were investigated for three relatives who carried the Swedish APP(670, 671) mutation which causes overproduction of Abeta40 and Abeta42. They differed in terms of APOE genotype, age at the onset of dementia, and disease duration (P1: epsilon2/3, age 57, 11 years; P2: epsilon2/3, age 61, 5 years; P3: epsilon4/4, age 44, 12 years). For each subject, paraffin-embedded sections from diverse anatomically and cytoarchitectonically well-preserved regions were stained using the modified Bielschowsky method. Neurofibrillary tangles (NFT) and neuritic plaques (NP) were counted, and the area occupied by plaque estimated (%NP). In addition, sections from the medial frontal gyrus were stained with monoclonal antibodies to APOE. The regional patterns of neurofibrillary changes were consistent with those for late-onset AD. Longer disease duration was associated with further accumulations in earlier-affected areas, with superficial cortical layers consistently containing higher %NP than deep layers. APOE epsilon4/4 was associated with deeper limbic and frontal NFT, with an excess of NP (especially in the outer parietal cortex) which stained heavily for APOE - as well as with very early onset. APP(670, 671) mutation carriers demonstrate regional brain neurofibrillary changes characteristic of late-onset Alzheimer's disease with evidence for more Abeta deposition for epsilon4/4 than epsilon2/3. This raises the possibility that early Braak Stage I-II lesions might also follow this pattern of promotion.
Bogdanovic
N
N
NEUROTEC, Geriatric Section, KI, NOVUM, KFC, level 4, S-14186, Stockholm, Sweden. brainbank@kfc.hs.sll.se
Corder
Elizabeth
E
Lannfelt
L
L
Winblad
B
B
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009454:Neurofibrils / Q000473:pathology; D017354:Point Mutation; D011110:Polymorphism, Genetic; D013548:Sweden
D001057:Apolipoproteins E