Synaptic Loss, ER Stress and Neuro-Inflammation Emerge Late in the Lateral Temporal Cortex and Associate with Progressive Tau Pathology in Alzheimer’s Disease
| العنوان: | Synaptic Loss, ER Stress and Neuro-Inflammation Emerge Late in the Lateral Temporal Cortex and Associate with Progressive Tau Pathology in Alzheimer’s Disease |
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| المؤلفون: | Heather Buchanan, Karolína Tothová, Miroslava Katsur, David J. Koss, Murray Mackay, Bettina Platt, Kerri Palmer |
| المصدر: | Molecular Neurobiology |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Amyloid beta, Neuroscience (miscellaneous), tau Proteins, Unfolded protein response, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cognition, 0302 clinical medicine, Alzheimer Disease, mental disorders, medicine, Humans, Amyloid-β, Cognitive Dysfunction, Cognitive decline, Neuroinflammation, Aged, Aged, 80 and over, Inflammation, Temporal cortex, Amyloid beta-Peptides, biology, Glial fibrillary acidic protein, business.industry, Brain, Human brain, Endoplasmic Reticulum Stress, Synapse, 030104 developmental biology, medicine.anatomical_structure, Neurology, Neuro-inflammation, biology.protein, Synaptophysin, Original Article, Female, Tau, business, Alzheimer’s disease, Biomarkers, 030217 neurology & neurosurgery |
| الوصف: | The complex multifactorial nature of AD pathogenesis has been highlighted by evidence implicating additional neurodegenerative mechanisms, beyond that of amyloid-β (Aβ) and tau. To provide insight into cause and effect, we here investigated the temporal profile and associations of pathological changes in synaptic, endoplasmic reticulum (ER) stress and neuro-inflammatory markers. Quantifications were established via immunoblot and immunohistochemistry protocols in post-mortem lateral temporal cortex (n = 46). All measures were assessed according to diagnosis (non-AD vs. AD), neuropathological severity (low (Braak ≤ 2) vs. moderate (3–4) vs. severe (≥ 5)) and individual Braak stage, and were correlated with Aβ and tau pathology and cognitive scores. Postsynaptic PSD-95, but not presynaptic synaptophysin, was decreased in AD cases and demonstrated a progressive decline across disease severity and Braak stage, yet not with cognitive scores. Of all investigated ER stress markers, only phospho-protein kinase RNA-like ER kinase (p-PERK) correlated with Braak stage and was increased in diagnosed AD cases. A similar relationship was observed for the astrocytic glial fibrillary acidic protein (GFAP); however, the associated aquaporin 4 and microglial Iba1 remained unchanged. Pathological alterations in these markers preferentially correlated with measures of tau over those related to Aβ. Notably, GFAP also correlated strongly with Aβ markers and with all assessments of cognition. Lateral temporal cortex-associated synaptic, ER stress and neuro-inflammatory pathologies are here determined as late occurrences in AD progression, largely associated with tau pathology. Moreover, GFAP emerged as the most robust indicator of disease progression, tau/Aβ pathology, and cognitive impairment. Electronic supplementary material The online version of this article (10.1007/s12035-020-01950-1) contains supplementary material, which is available to authorized users. |
| تدمد: | 1559-1182 0893-7648 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9bcc5e608059e34fc48ec67183e6a8c1 https://doi.org/10.1007/s12035-020-01950-1 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9bcc5e608059e34fc48ec67183e6a8c1 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15591182 08937648 |
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