Affiliations: Department of Psychiatry, The Mount Sinai School of
Medicine, New York, NY, 10029-6574, USA | Department of Pathology, The Mount Sinai School of
Medicine, New York, NY, 10029-6574, USA
Note: [] Corresponding author: Giulio Maria Pasinetti, M.D., Ph.D.,
Neuroinflammation Research Laboratories, Department of Psychiatry, Box 1230,
Mount Sinai Medical Center, One Gustave L. Levy Place, New York, New York
10029, USA. Tel.: +1 212 241 5579; Fax: +1 212 876 9042; E-mail:
giulio.pasinetti@mssm.edu
Abstract: The role of microglia-mediated inflammation in the progression of
Alzheimer's disease (AD) neuropathology remains unclear. In this study,
postmortem brain sections from AD and control cases were subjected to Human
Leukocyte Antigen (HLA)-DR immunohistochemistry to examine microglia activation
in the progression of AD assessed by pre-mortem clinical dementia rating (CDR)
and postmortem pathological manifestations of neuritic plaque (NP) and
neurofibrillary tangle (NT) according to the Consortium to Establish a Registry
for Alzheimer's Disease (CERAD). In both gray and white matter of the
entorhinal cortex (EC) and HLA-DR immunostaining increased with the progression
of CDR or CERAD NP, and to a lesser degree with CERAD NT. Between CDR stages
HLA-DR significance was found in moderate (CDR 2) to severe dementia (CDR 5)
where as between CERAD NP stages staining increased significantly from NP 0 (no
plaque) to NP 1 (sparse plaques), suggesting increased microglia activation
begins with amyloid NP deposition. In the hippocampus, a significant increase
in microglia immunostaining was found in the pyramidal cell layer of CA1 as
early as CDR 1, and in the upper molecular layer of the dentate gyrus in CDR
0.5. This increase continues with the progression of CDR and reaches maximum in
CDR 5. When assessed by CERAD NP stages however, a significant increase in
microglia immunostaining was found only in mid-to-late stages (NP 3) and
reduced staining was seen in NP 5. These results suggest that microglia
activation increases with the progression of AD, with the increase varying
depending on the involved brain region.
