Bibliographic Details
| Title: |
Sex-Specific Adaptations in Alzheimer’s Disease and Ischemic Stroke: A Longitudinal Study in Male and Female APPswe/PS1dE9 Mice |
| Authors: |
Klara J. Lohkamp, Nienke Timmer, Gemma Solé Guardia, Justin Shenk, Vivienne Verweij, Bram Geenen, Pieter J. Dederen, Lieke Bakker, Cansu Egitimci, Rengin Yoldas, Minou Verhaeg, Josine Kothuis, Desirée Nieuwenhuis, Maximilian Wiesmann, Amanda J. Kiliaan |
| Source: |
Life, Vol 15, Iss 3, p 333 (2025) |
| Publisher Information: |
MDPI AG, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Science |
| Subject Terms: |
Alzheimer’s disease, stroke, sex differences, MRI, cerebral blood flow, cognition neuroinflammation, Science |
| More Details: |
The long-term impact of stroke on Alzheimer’s disease (AD) progression, particularly regarding sex-specific differences, remains unknown. Using a longitudinal study design, we investigated transient middle cerebral artery occlusion in 3.5-month-old APPswe/PS1dE9 (APP/PS1) and wild-type mice. In vivo, we assessed behavior, cerebral blood flow (CBF), and structural integrity by neuroimaging, as well as post-mortem myelin integrity (polarized light imaging, PLI), neuroinflammation, and amyloid beta (Aβ) deposition. APP/PS1 mice exhibited cognitive decline, white matter degeneration (reduced fractional anisotropy (FA) via diffusion tensor imaging (DTI)), and decreased myelin density via PLI. Despite early hypertension, APP/PS1 mice showed only sporadic hypoperfusion. Cortical thickening and hippocampal hypertrophy likely resulted from Aβ accumulation and neuroinflammation. Stroke-operated mice retained cognition despite cortical thinning and hippocampal atrophy due to cerebrovascular adaptation, including increased CBF in the hippocampus and thalamus. Stroke did not worsen AD pathology, nor did AD exacerbate stroke outcomes. Sex differences were found: female APP/PS1 mice had more severe Aβ deposition, hyperactivity, lower body weight, and reduced CBF but less neuroinflammation, suggesting potential neuroprotection. These findings highlight white matter degeneration and Aβ pathology as key drivers of cognitive decline in AD, with stroke-related deficits mitigated by (cerebro)vascular adaptation. Sex-specific therapies are crucial for AD and stroke. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2075-1729 |
| Relation: |
https://www.mdpi.com/2075-1729/15/3/333; https://doaj.org/toc/2075-1729 |
| DOI: |
10.3390/life15030333 |
| Access URL: |
https://doaj.org/article/a04f432f0c954fbaa2022e00663c09a4 |
| Accession Number: |
edsdoj.04f432f0c954fbaa2022e00663c09a4 |
| Database: |
Directory of Open Access Journals |
|
Full text is not displayed to guests. |
Login for full access.
|
