Publications by authors named "Tim Bathe"

Background: Variants in the gene have been identified as a risk factor for late-onset Alzheimer's disease and are linked to decreased white matter integrity in healthy adults. However, the specific role for clusterin in myelin maintenance in the context of Alzheimer's disease remains unclear.

Methods: We employed a combination of immunofluorescence and transmission electron microscopy techniques, primary culture of OPCs, and an animal model of Alzheimer's disease.

View Article and Find Full Text PDF

Neuroinflammation plays an important role in the pathological cascade of Alzheimer's disease (AD) along with aggregation of extracellular amyloid-β (Aβ) plaques and intracellular aggregates of tau protein. In animal models of amyloidosis, local immune activation is centered around Aβ plaques, which are usually of uniform morphology, dependent on the transgenic model used. In postmortem human brains a diversity of Aβ plaque morphologies is seen including diffuse plaques (non-neuritic plaques, non-NP), dense-core plaques, cotton-wool plaques, and NP.

View Article and Find Full Text PDF
Article Synopsis
  • - Recent studies suggest that systemic infections, like COVID-19, may worsen Alzheimer's disease (AD) in vulnerable aging populations, prompting this research on brains from AD patients who survived COVID-19 compared to those who did not.
  • - Post-mortem analysis revealed that COVID-AD patients exhibited higher levels of amyloid beta (Aβ) in specific brain regions and significant disruptions in microglial and astrocytic function compared to non-COVID AD patients.
  • - Findings indicate lasting effects of COVID-19 on neuroimmune responses and glial health in AD patients, potentially contributing to disease progression long after infection, particularly involving pathways related to myelination and oligodendrocyte dysregulation.
View Article and Find Full Text PDF

Background: White matter loss is a well-documented phenomenon in Alzheimer's disease (AD) patients that has been recognized for decades. However, the underlying reasons for the failure of oligodendrocyte progenitor cells (OPCs) to repair myelin deficits in these patients remain elusive. A single nucleotide polymorphism (SNP) in Clusterin has been identified as a risk factor for late-onset Alzheimer's disease and linked to a decrease in white matter integrity in healthy adults, but its specific role in oligodendrocyte function and myelin maintenance in Alzheimer's disease pathology remains unclear.

View Article and Find Full Text PDF

The disease-specific accumulation of pathological proteins has long been the major focus of research in neurodegenerative diseases (ND), including Alzheimer's disease (AD) and related dementias (RD), but the recent identification of a multitude of genetic risk factors for ND in immune-associated genes highlights the importance of immune processes in disease pathogenesis and progression. Studies in animal models have characterized the local immune response to disease-specific proteins in AD and ADRD, but due to the complexity of disease processes and the co-existence of multiple protein pathologies in human donor brains, the precise role of immune processes in ND is far from understood. To better characterize the interplay between different extracellular and intracellular protein pathologies and the brain's intrinsic immune system in ND, we set out to comprehensively profile the local immune response in postmortem brain samples of individuals with "pure" beta-Amyloid and tau pathology (AD), "pure" α-Synuclein pathology in Lewy body diseases (LBD), as well as cases with Alzheimer's disease neuropathological changes (ADNC) and Lewy body pathology (MIX).

View Article and Find Full Text PDF

Extracellular amyloid-β (Aβ) plaques and intracellular aggregates of tau protein in form of neurofibrillary tangles (NFT) are pathological hallmarks of Alzheimer's disease (AD). The exact mechanism how these two protein aggregates interact in AD is still a matter of debate. Neuritic plaques (NP), a subset of Aβ plaques containing dystrophic neurites (DN), are suggested to be unique to AD and might play a role in the interaction of Aβ and tau.

View Article and Find Full Text PDF

Apolipoprotein (APOE) E4 isoform is a major risk factor of Alzheimer's disease and contributes to metabolic and neuropathological abnormalities during brain aging. To provide insights into whether APOE4 genotype is related to tau-associated neurodegeneration, we have generated human P301S mutant tau transgenic mice (PS19) that carry humanized APOE alleles (APOE2, APOE3 or APOE4). In aging mice that succumbed to paralysis, PS19 mice homozygous for APOE3 had the longest lifespan when compared to APOE4 and APOE2 homozygous mice (APOE3 > APOE4 ~ APOE2).

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessionqbu9u4p10494ffm1k334sfnc6mja3pf7): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once