Naslov
Distinct microglia profile in Creutzfeldt-Jakob disease and Alzheimer's disease is independent of disease kinetics

Autori
Krbot, Katarina ; Hermann, Peter ; Krbot Skorić, Magdalena ; Zerr, Inga ; Sepulveda‐Falla, Diego ; Goebel, Stefan ; Matschke, Jakob ; Krasemann, Susanne ; Glatzel, Markus

Izvornik
Neuropathology (0919-6544) 38 (2018), 6; 591-600

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
TMEM119 ; microglia ; monocyte-derived macrophages ; rapidly progressive Alzheimer's disease ; sporadic Creutzfeldt-Jakob disease

Sažetak
Activated microglia represent a common pathological feature of neurodegenerative diseases. Sporadic Creutzfeldt-Jakob disease (sCJD) patients show more pronounced microglial activation than Alzheimer's disease (AD) patients. Whether these differences are due to differences in disease kinetics or represent disease-specific changes is unknown. We investigated microglial phenotypes in brains of rapidly progressive AD (rpAD) and sCJD patients matched for clinical presentation, including disease duration. We immunostained the frontal cortex, basal ganglia and cerebellum in 16 patients with rpAD and sCJD using antibodies against markers of microglia and recruited monocytes (ionized calcium-binding adaptor molecule 1, human leukocyte antigen DPQR, Cluster of Differentiation 68), an antibody unique to brain-resident microglia (transmembrane protein 119 (TMEM119)), in addition to antibodies against a marker of astrocytes (glial fibrillary acidic protein), amyloid-β (Aβ) and pathological prion protein. rpAD patients showed a distinct microglial phenotype with a high abundance of TMEM119-positive microglia in all investigated regions. Presence of Aβ deposits seen in a sCJD patient with concomitant deposition of Aβ led to increase of TMEM119-positive microglia. Our data suggest that in rpAD, activation of brain- resident microglia significantly contributes to microgliosis, whereas in sCJD the TMEM119 signature of resident microglial cells is barely detectable. This is irrespective of disease duration and may indicate disease-specific microglial reaction.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA