Neurones and microglia in central nervous system immune response to degenerative processes. Part 1: Alzheimer's disease and Lewy body variant of Alzheimer's disease. Quantitative study.
The quantitative correlation between neurone loss and brain immune response, assessed by intensity of microglia inflammatory reaction in cortical association area and limbic cortex, was investigated and compared in previously immunohistochemistry (IHC) and ultrastructural confirmed 11 cases of Alzheimer's disease (AD), 7 cases mixed form of Dementia with AD findings and Lewy bodies (AD/DLB) reported, in accordance with Consortium on Dementia, as Lewy body variant of AD (LBV) and 6 non-demented autopsy control cases from 63 to 86 years old. In the present work we investigated association and limbic cortical areas linked with memory mechanisms; there are regions characterised by early distribution of IHC confirmed AD and DLB/AD (LBV) markers, as well as a substantial physiological stability of neurone pool regardless of age. The results indicated that AD and LBV differ in their neurone loss intensity and inflammatory reaction, with much higher intensity in AD. In Alzheimer's disease, neurone loss in association temporal cortex made up 51% of control values with simultaneous 8-fold increase in the density of MHC II-positive activated microglia, whereas in LBV, both the loss of neurone density and the increase in activated microglia density, was not so high (up to 41% and 4-5-fold, respectively). Changes in the limbic cortex were less pronounced. A strong correlation in the clinical material between neurone loss and microglia activation in both processes, especially in AD (r = 0.73), speaks in favour of the hypothesis on the neuronal immune surveillance and arousal of immune brain response in conditions of declining control, due to significant neurone loss in the neurodegenerative process. The inflammatory reaction of MHC II-immunoreactive microglia, concomitant with neurodegenerative process, seems to be a consequence of increased immune response due to loss of neurones and weakening of their control upon immunosurveillance in central nervous system.
Szpak
G M
GM
Department of Neuropathology, Institute of Psychiatry and Neurology, Warszawa, Poland.
Lechowicz
W
W
Lewandowska
E
E
Bertrand
E
E
Wierzba-Bobrowicz
T
T
Gwiazda
E
E
Schmidt-Sidor
B
B
Dymecki
J
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D003593:Cytoplasm / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000648:ultrastructure; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D006680:HLA Antigens; D014157:Transcription Factors; C077171:HIVEP2 protein, human