Neocortical and hippocampal TREM2 protein levels during the progression of Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:54

Article

Perez, Sylvia E.^1,2  Nadeem, Muhammad^1,2  He, Bin^1,2  Miguel, Jennifer C.^1,2  Malek-Ahmadi, Michael H.³  Chen, Kewei³  Mufson, Elliott J.^1,2 

[1] Barrow Neurol Inst, Dept Neurobiol, Phoenix, AZ 85013 USA

[2] Barrow Neurol Inst, Dept Neurol, Alzheimers Dis Res Lab, Phoenix, AZ 85013 USA

[3] Banner Alzheimers Inst, Phoenix, AZ USA

关键词: Alzheimer's disease;    Mild cognitive impairment;    TREM2;    Microglia;    Tau;    Amyloid;    Immunohistochemistry;    Western-blot;   

DOI  :  10.1016/j.neurobiolaging.2017.02.012

来源: Elsevier

【 摘 要 】

Heterozygous triggering receptor expressed on myeloid cells (TREM2) mutations are an Alzheimer's disease (AD) risk factor. Nonmutated TREM2 dysregulation occurs in AD brain. Whether TREM2 is altered in prodromal AD remains unknown. Western blotting was used to determine levels of TREM2 (similar to 25 kDa) and Iba1 in the frontal cortex and TREM2 in the hippocampus from people who died with an antemortem clinical diagnosis of non- and mild-cognitive impairment, mild/moderate AD, and severe AD (sAD). Immunohistochemistry defined the relationship between amyloid and Iba1 profiles. Polymerase chain reaction analysis revealed that all subjects did not carry the most common R47H TREM2 variant. TREM2 was significantly upregulated in sAD frontal cortex but stable in hippocampus. Frontal TREM2 mRNA and protein level patterns were similar but not significantly different. Iba1 immunopositive microglia counts increased significantly in frontal cortex containing plaques in sAD. TREM2 and Iba1 levels were not associated with plaques, tangles, neuropathological criteria, or cognitive performance. Frontal cortex TREM2 upregulation is a late event and may not play a major role early in the pathogenesis of the disease. (C) 2017 Elsevier Inc. All rights reserved.

【 授权许可】

Free