Amyloid-beta, alpha-synuclein and tau aggregated co-pathologies enhance neuropathology and neuroinflammation DOI Creative Commons
J. Webster, William J. Stone, Yating Yang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 13, 2024

Abstract Lewy pathology due to alpha-synuclein (α-syn) inclusions is one of the major hallmarks Parkinson’s Disease (PD). β-Amyloid (Aβ) and phosphorylated-tau, pathologies usually found in Alzheimer’s (AD), have also been implicated PD, with over 50% patients exhibited co-expression these proteins (co-pathologies). In both AD PD postmortem tissue, neuroinflammation – activation microglia resident macrophages infiltration immune cells from periphery, including T monocytes–are drivers neurodegeneration. However, how contribute inflammatory response overall neurodegenerative disease phenotype remains unknown. To understand drives neuropathology, we developed a novel co-pathology model by stereotaxically injecting α-syn pre-formed fibrils (PFFs) into striatum, AAV-double mut tau virus entorhinal cortex, 3-month-old J20 transgenic mice Aβ pathology. We analyzed cell populations brain periphery at 3 months post-induction (3MPI). At 6MPI, neuronal loss hippocampus substantia nigra pars compacta were assessed along pathological protein deposition. 3MPI, mouse begins exhibit enhanced load cortex hippocampus. There was robust neuroinflammatory interconnected regions, increased microglial number, changes markers, cells. This synergistic model, compared individual models, supporting hypothesis that collectively may drive progression disease.

Язык: Английский

Amyloid-beta, alpha-synuclein and tau aggregated co-pathologies enhance neuropathology and neuroinflammation DOI Creative Commons
J. Webster, William J. Stone, Yating Yang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 13, 2024

Abstract Lewy pathology due to alpha-synuclein (α-syn) inclusions is one of the major hallmarks Parkinson’s Disease (PD). β-Amyloid (Aβ) and phosphorylated-tau, pathologies usually found in Alzheimer’s (AD), have also been implicated PD, with over 50% patients exhibited co-expression these proteins (co-pathologies). In both AD PD postmortem tissue, neuroinflammation – activation microglia resident macrophages infiltration immune cells from periphery, including T monocytes–are drivers neurodegeneration. However, how contribute inflammatory response overall neurodegenerative disease phenotype remains unknown. To understand drives neuropathology, we developed a novel co-pathology model by stereotaxically injecting α-syn pre-formed fibrils (PFFs) into striatum, AAV-double mut tau virus entorhinal cortex, 3-month-old J20 transgenic mice Aβ pathology. We analyzed cell populations brain periphery at 3 months post-induction (3MPI). At 6MPI, neuronal loss hippocampus substantia nigra pars compacta were assessed along pathological protein deposition. 3MPI, mouse begins exhibit enhanced load cortex hippocampus. There was robust neuroinflammatory interconnected regions, increased microglial number, changes markers, cells. This synergistic model, compared individual models, supporting hypothesis that collectively may drive progression disease.

Язык: Английский

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