Mild Microglial Responses in the Cortex and Perivascular Macrophage Infiltration in Subcortical White Matter in Dogs with Age-Related Dementia Modelling Prodromal Alzheimer's Disease
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Mild Microglial Responses in the Cortex and Perivascular Macrophage Infiltration in Subcortical White Matter in Dogs with Age-Related Dementia Modelling Prodromal Alzheimer's Disease. / Thomsen, Barbara Blicher; Madsen, Cecilie; Krohn, Katrine Tækker; Thygesen, Camilla; Schütt, Trine; Metaxas, Athanasios; Darvesh, Sultan; Agerholm, Jørgen Steen; Wirenfeldt, Martin; Berendt, Mette; Finsen, Bente.
I: Journal of Alzheimer's Disease, Bind 82, Nr. 2, 2021, s. 575-592.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Mild Microglial Responses in the Cortex and Perivascular Macrophage Infiltration in Subcortical White Matter in Dogs with Age-Related Dementia Modelling Prodromal Alzheimer's Disease
AU - Thomsen, Barbara Blicher
AU - Madsen, Cecilie
AU - Krohn, Katrine Tækker
AU - Thygesen, Camilla
AU - Schütt, Trine
AU - Metaxas, Athanasios
AU - Darvesh, Sultan
AU - Agerholm, Jørgen Steen
AU - Wirenfeldt, Martin
AU - Berendt, Mette
AU - Finsen, Bente
N1 - Publisher Copyright: © 2021 - The authors. Published by IOS Press.
PY - 2021
Y1 - 2021
N2 - Background: Microglia contribute to Alzheimer's disease (AD) pathogenesis by clearing amyloid-β (Aβ) and driving neuroinflammation. Domestic dogs with age-related dementia (canine cognitive dysfunction (CCD)) develop cerebral amyloidosis like humans developing AD, and studying such dogs can provide novel information about microglial response in prodromal AD. Objective: The aim was to investigate the microglial response in the cortical grey and the subcortical white matter in dogs with CCD versus age-matched cognitively normal dogs. Methods: Brains from aged dogs with CCD and age-matched controls without dementia were studied. Cases were defined by dementia rating score. Brain sections were stained for Aβ, thioflavin S, hyperphosphorylated tau, and the microglial-macrophage ionized calcium binding adaptor molecule 1 (Iba1). Results were correlated to dementia rating score and tissue levels of Aβ. Results: Microglial numbers were higher in the Aβ plaque-loaded deep cortical layers in CCD versus control dogs, while the coverage by microglial processes were comparable. Aβ plaques were of the diffuse type and without microglial aggregation. However, a correlation was found between the %Iba1 area and insoluble Aβ 42 and N-terminal pyroglutamate modified Aβ(N3pE)-42. The %Iba1 area was higher in white matter, showing phosphorylation of S396 tau, versus grey matter. Perivascular macrophage infiltrates were abundant in the white matter particularly in CDD dogs. Conclusion: The results from this study of the microglial-macrophage response in dogs with CCD are suggestive of relatively mild microglial responses in the Aβ plaque-loaded deep cortical layers and perivascular macrophage infiltrates in the subcortical white matter, in prodromal AD.
AB - Background: Microglia contribute to Alzheimer's disease (AD) pathogenesis by clearing amyloid-β (Aβ) and driving neuroinflammation. Domestic dogs with age-related dementia (canine cognitive dysfunction (CCD)) develop cerebral amyloidosis like humans developing AD, and studying such dogs can provide novel information about microglial response in prodromal AD. Objective: The aim was to investigate the microglial response in the cortical grey and the subcortical white matter in dogs with CCD versus age-matched cognitively normal dogs. Methods: Brains from aged dogs with CCD and age-matched controls without dementia were studied. Cases were defined by dementia rating score. Brain sections were stained for Aβ, thioflavin S, hyperphosphorylated tau, and the microglial-macrophage ionized calcium binding adaptor molecule 1 (Iba1). Results were correlated to dementia rating score and tissue levels of Aβ. Results: Microglial numbers were higher in the Aβ plaque-loaded deep cortical layers in CCD versus control dogs, while the coverage by microglial processes were comparable. Aβ plaques were of the diffuse type and without microglial aggregation. However, a correlation was found between the %Iba1 area and insoluble Aβ 42 and N-terminal pyroglutamate modified Aβ(N3pE)-42. The %Iba1 area was higher in white matter, showing phosphorylation of S396 tau, versus grey matter. Perivascular macrophage infiltrates were abundant in the white matter particularly in CDD dogs. Conclusion: The results from this study of the microglial-macrophage response in dogs with CCD are suggestive of relatively mild microglial responses in the Aβ plaque-loaded deep cortical layers and perivascular macrophage infiltrates in the subcortical white matter, in prodromal AD.
KW - Alzheimer's disease
KW - Amyloid-β
KW - Animal model
KW - Dementia
KW - Macrophages
KW - Microglia
KW - Neuroinflammation
U2 - 10.3233/JAD-210040
DO - 10.3233/JAD-210040
M3 - Journal article
C2 - 34057083
AN - SCOPUS:85111384704
VL - 82
SP - 575
EP - 592
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 2
ER -
ID: 275830615