Premorbid effects of APOE on synaptic proteins in human temporal neocortex.
APOE affects the risk of Alzheimer's disease (AD) and course of several other neurologic diseases. Experimental studies suggest that APOE influences synaptogenesis. We measured the concentration of two presynaptic proteins, synaptophysin and syntaxin 1, and also postsynaptic density-95 (PSD95), in superior temporal cortex from 42 AD and 160 normal brains, and determined the APOE genotypes. The concentration of both presynaptic proteins was approximately two-thirds lower in AD than normal brains and that of PSD95 one-third lower. No effect of APOE on synaptic proteins was found in advanced AD. However, in normal brain, epsilon4 was associated with lower concentrations of all three synaptic proteins and epsilon2 with significantly elevated PSD95 (p=0.03). A combined measure of synaptic proteins showed a significant linear decrease from epsilon2 through epsilon3 to varepsilon4 (p=0.01). APOE influences the concentration of synaptic proteins in normal superior temporal cortex and may thereby affect the response to injury, and the risk and outcome of a range of neurologic diseases.
Department of Neuropathology, University of Bristol Institute of Clinical Neurosciences, Frenchay Hospital, Bristol BS16 1LE, UK. seth.love@bris.ac.uk
Seth
S
Love
L Khai
LK
Siew
David
D
Dawbarn
Gordon K
GK
Wilcock
Yoav
Y
Ben-Shlomo
Shelley J
SJ
Allen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D016001:Confidence Intervals; D000076122:Disks Large Homolog 4 Protein; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011180:Postmortem Changes; D050765:Qa-SNARE Proteins / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism*
D001057:Apolipoproteins E; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; D016708:Synaptophysin