Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer's disease

TY - JOUR

T1 - Seed-induced Aβ deposits in the corpus callosum disrupt white matter integrity in a mouse model of Alzheimer's disease

AU - Aires, Vanessa

AU - Ziegler-Waldkirch, Stephanie

AU - Friesen, Marina

AU - Reichardt, Wilfried

AU - Erny, Daniel

AU - Loreth, Desiree

AU - Harborne, Andrew

AU - Kretz, Oliver

AU - von Elverfeldt, Dominik

AU - Meyer-Luehmann, Melanie

N1 - Copyright © 2022 Aires, Ziegler-Waldkirch, Friesen, Reichardt, Erny, Loreth, Harborne, Kretz, von Elverfeldt and Meyer-Luehmann.

PY - 2022/8/8

Y1 - 2022/8/8

N2 - Neuropathologically, Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta peptide (Aβ) and subsequent formation of the so-called Aβ plaques. Along with neuronal loss, previous studies report white matter anomalies and corpus callosum (CC) atrophy in AD patients. Notably, perturbations in the white matter can be observed years before expected disease onset, suggesting that early stages of disease progression play a role in AD-associated loss of myelin integrity. Through seed-induced deposition of Aβ, we are able to examine alterations of central nervous system (CNS) integrity during the initial stages of plaque formation. In this study, we investigate the impact of Aβ seeding in the CC utilizing various imaging techniques as well as quantitative gene expression analysis and demonstrate that Aβ deposits result in an imbalance of glial cells in the CC. We found increased amounts of phagocytic microglia and reactive astrocytes, while oligodendrocyte progenitor cell (OPC) numbers were reduced. Moreover, white matter aberrations adjacent to the Aβ seeding were observed together with an overall decline in callosal myelination. This data indicate that the initial stages of plaque formation induce oligodendrocyte dysfunction, which might ultimately lead to myelin loss.

AB - Neuropathologically, Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta peptide (Aβ) and subsequent formation of the so-called Aβ plaques. Along with neuronal loss, previous studies report white matter anomalies and corpus callosum (CC) atrophy in AD patients. Notably, perturbations in the white matter can be observed years before expected disease onset, suggesting that early stages of disease progression play a role in AD-associated loss of myelin integrity. Through seed-induced deposition of Aβ, we are able to examine alterations of central nervous system (CNS) integrity during the initial stages of plaque formation. In this study, we investigate the impact of Aβ seeding in the CC utilizing various imaging techniques as well as quantitative gene expression analysis and demonstrate that Aβ deposits result in an imbalance of glial cells in the CC. We found increased amounts of phagocytic microglia and reactive astrocytes, while oligodendrocyte progenitor cell (OPC) numbers were reduced. Moreover, white matter aberrations adjacent to the Aβ seeding were observed together with an overall decline in callosal myelination. This data indicate that the initial stages of plaque formation induce oligodendrocyte dysfunction, which might ultimately lead to myelin loss.

U2 - 10.3389/fncel.2022.862918

DO - 10.3389/fncel.2022.862918

M3 - SCORING: Journal article

C2 - 36003141

VL - 16

JO - FRONT CELL NEUROSCI

JF - FRONT CELL NEUROSCI

SN - 1662-5102

M1 - 862918

ER -