Inflammation, A beta deposition, and neurofibrillary tangle formation as correlates of Alzheimer's disease neurodegeneration.
We evaluated entorhinal cortex and superior frontal gyrus for hallmarks of Alzheimer's disease (AD) pathology, including inflammation, in three patient sets: AD patients, nondemented elderly patients with few or no neurofibrillary tangles (NFTs) and amyloid beta peptide (A beta) deposits, i.e. normal controls (NC), and nondemented elderly patients with profuse entorhinal cortex NFTs and neocortical A beta deposits, i.e. high pathology controls (HPC). Membrane attack complex (C5b-9) immunoreactivity and immune activation of microglia (MHCII expression) were used as general markers for inflammation. Compared to NC patients, AD patients exhibited significant cortical synapse loss, A beta deposition, NFT formation, and inflammation. HPC patients also had significantly elevated A beta deposition and NFT formation, but there was no evidence of synapse loss and little or no evidence of inflammation. Across patients and brain regions the measures of inflammation each accounted for significant percentages of the variance in synaptophysin immunoreactivity and each was more highly correlated with synapse estimates than NFT formation or A beta deposition.
Lue
L F
LF
L.J. Roberts Center, Sun Health Research Institute, Sun City, AZ 85372, USA.
Brachova
L
L
Civin
W H
WH
Rogers
J
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D015415:Biomarkers; D015153:Blotting, Western; D018728:Entorhinal Cortex / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000737:chemistry; D009410:Nerve Degeneration / Q000502:physiology; D009443:Neuritis / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000737:chemistry* / Q000276:immunology
D016229:Amyloid beta-Peptides; D015415:Biomarkers