Association of glial tau pathology and LATE-NC in the ageing brain

Neurobiol Aging. 2022 Nov:119:77-88. doi: 10.1016/j.neurobiolaging.2022.07.010. Epub 2022 Jul 31.

Abstract

Ageing-related pathologies of the brain include neurofibrillary tangles, argyrophilic grains, ageing-related tau astrogliopathy (ARTAG), limbic-predominant age-related TDP-43 encephalopathy-neuropathological change (LATE-NC), vascular pathology and corpora amylacea. This study used an unbiased approach to evaluate a broad range of pathologies in an unselected European community-dwelling ageing cohort of 101 individuals (77-90 years). Pathological alterations observed included neurofibrillary tangles and corpora amylacea in all cases, ARTAG (79%), Thal amyloid-β phase >1 (60%), cerebral amyloid angiopathy (39%), Lewy bodies (22%), LATE-NC (21%), oligodendroglial tau-positive coiled bodies (33%), and argyrophilic grains (15%). We demonstrate association of LATE-NC with the previously unappreciated age-related tau oligodendrogliopathy (ARTOG) and highlight the association of LATE-NC with various ARTAG types pointing toward common pathogenic aspects. Only neurofibrillary tangles and LATE-NC were associated with cognitive decline. This study broadens the spectrum of age-related brain pathologies and highlights a novel ageing-related tau pathology in oligodendroglia. Results from this study suggest overlapping pathogenic mechanisms between LATE-NC and glial tau pathologies in the medial temporal lobe.

Keywords: ARTAG; Ageing; Limbic Age-related TDP-43 Encephalopathy-neuropathological change; Mixed pathology; Oligodendroglia; Tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging* / genetics
  • Aging* / pathology
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / pathology
  • Brain / metabolism
  • Brain / pathology
  • DNA-Binding Proteins / metabolism
  • Dementia* / genetics
  • Dementia* / pathology
  • Humans
  • Neurofibrillary Tangles / genetics
  • Neurofibrillary Tangles / pathology
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Oligodendroglia* / metabolism
  • Oligodendroglia* / pathology
  • TDP-43 Proteinopathies* / genetics
  • TDP-43 Proteinopathies* / pathology
  • Temporal Lobe* / metabolism
  • Temporal Lobe* / pathology
  • tau Proteins* / genetics
  • tau Proteins* / metabolism

Substances

  • DNA-Binding Proteins
  • tau Proteins

Supplementary concepts

  • limbic-predominant age-related TDP-43 encephalopathy