The hippocampal longitudinal axis-relevance for underlying tau and TDP-43 pathology

Neurobiol Aging. 2018 Oct:70:1-9. doi: 10.1016/j.neurobiolaging.2018.05.035. Epub 2018 Jun 1.

Abstract

Recent studies suggest that hippocampus has different cortical connectivity and functionality along its longitudinal axis. We sought to elucidate the possible different pattern of atrophy in longitudinal axis of hippocampus between Amyloid/Tau pathology and TDP-43-pathies. Seventy-three presenile subjects were included: Amyloid/Tau group (33 Alzheimer's disease with confirmed cerebrospinal fluid [CSF] biomarkers), probable TDP-43 group (7 semantic variant progressive primary aphasia, 5 GRN and 2 C9orf72 mutation carriers) and 26 healthy controls. We conducted a region-of-interest voxel-based morphometry analysis on the hippocampal longitudinal axis, by contrasting the groups, covarying with CSF biomarkers (Aβ42, total tau, p-tau) and covarying with episodic memory scores. Amyloid/Tau pathology affected mainly posterior hippocampus while anterior left hippocampus was more atrophied in probable TDP-43-pathies. We also observed a significant correlation of posterior hippocampal atrophy with Alzheimer's disease CSF biomarkers and visual memory scores. Taken together, these data suggest that there is a potential differentiation along the hippocampal longitudinal axis based on the underlying pathology, which could be used as a potential biomarker to identify the underlying pathology in different neurodegenerative diseases.

Keywords: Alzheimer's disease; Frontotemporal dementia; Hippocampus; MRI; Memory; Semantic variant of progressive primary aphasia; TDP-43; Tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Aphasia, Primary Progressive / diagnostic imaging
  • Aphasia, Primary Progressive / pathology*
  • Biomarkers / cerebrospinal fluid
  • DNA-Binding Proteins / metabolism
  • Female
  • Hippocampus / diagnostic imaging
  • Hippocampus / pathology*
  • Humans
  • Male
  • Memory, Episodic
  • Middle Aged
  • Neuropsychological Tests
  • Retrospective Studies
  • TDP-43 Proteinopathies / metabolism
  • TDP-43 Proteinopathies / pathology*
  • tau Proteins / cerebrospinal fluid
  • tau Proteins / metabolism

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • MAPT protein, human
  • TARDBP protein, human
  • tau Proteins