Aging is the leading risk factor for idiopathic Alzheimer's disease (AD), indicating that normal aging processes promote AD and likely are present in the neurons in which AD pathogenesis originates. In AD, neurofibrillary tangles (NFTs) appear first in entorhinal cortex, implying that aging processes in entorhinal neurons promote NFT pathogenesis. Using electrophysiology and immunohistochemistry, we find pronounced aging-related Ca2 + dysregulation in rat entorhinal neurons homologous with the human neurons in which NFTs originate. Considering that humans recapitulate many aspects of animal brain aging, these results support the hypothesis that aging-related Ca2 + dysregulation occurs in human entorhinal neurons and promotes NFT pathogenesis.
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http://dx.doi.org/10.3233/JAD-180618 | DOI Listing |
Nat Commun
January 2025
Department of Neurosurgery, Xinqiao Hospital, Army Medical University, Chongqing, China.
Successful navigation relies on reciprocal transformations between spatial representations in world-centered (allocentric) and self-centered (egocentric) frames of reference. The neural basis of allocentric spatial representations has been extensively investigated with grid, border, and head-direction cells in the medial entorhinal cortex (MEC) forming key components of a 'cognitive map'. Recently, egocentric spatial representations have also been identified in several brain regions, but evidence for the coexistence of neurons encoding spatial variables in each reference frame within MEC is so far lacking.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
LCBC, University of Oslo, Oslo, Norway.
Background: Grid cells are spatially modulated cells in the entorhinal cortex (EC) that fire in a hexagonally patterned grid which tiles the environment. These cells are assumed important in human spatial navigation. The EC is vulnerable to neurodegenerative processes in both normal aging and Alzheimer's disease and decline in grid cell function may be a key factor in understanding age-related navigational decline.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
McGill University, Montreal, QC, Canada.
Background: Despite amyloid-β (Aβ) plaques and tau neurofibrillary tangles being recognized as major Alzheimer's Disease (AD) hallmarks, their synergistic contribution to neuronal activity remains unclear. We developed a neuroimaging-based personalized brain activity model to assess the in-vivo functional impact of AD pathophysiology. In previous reports, model-inferred neuronal excitability predicted disease progression (i.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Beth Israel Deaconess Medical Center, Boston, MA, USA.
Background: A significant proportion of individuals preserve cognitive function despite meeting neuropathological criteria for Alzheimer's disease (AD) at autopsy, known as cognitive resilience. We aimed to define the molecular and cellular signatures of cognitive resilience against AD.
Method: We integrated multi-modal data from the Religious Order Study and Memory and Aging Project (ROSMAP), including bulk (n = 631) and multi-regional single nucleus (n = 48) RNA sequencing.
Alzheimers Dement
December 2024
Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Background: An important hallmark of Alzheimer's Disease (AD) is the presence of neurofibrillary tangles (NFTs) composed of phosphorylated tau, which are commonly assessed using AT8 immunostains. Identifying additional markers to characterize the spectrum of NFT pathology is crucial for advancing our understanding and diagnosis of AD. This study introduces new potential markers to differentiate between tangles and healthy neurons.
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