White matter pathology isolates the hippocampal formation in Alzheimer's disease

Salat, D.H.; Tuch, D.S.; van der Kouwe, A.J.W.; Greve, D.N.; Pappu, V.; Lee, S.Y.; Hevelone, N.D.; Zaleta, A.K.; Growdon, J.H.; Corkin, S.; Fischl, B.; Rosas, H.D.

doi:10.1016/j.neurobiolaging.2008.03.013

Cited by 279Dementia and Cognitive Impairment ResearchAdvanced Neuroimaging Techniques and ApplicationsAlzheimer's disease research and treatments

White matter pathology isolates the hippocampal formation in Alzheimer's disease

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Salat, D.H., Tuch, D.S., van der Kouwe, A.J.W., Greve, D.N., Pappu, V., Lee, S.Y., Hevelone, N.D., Zaleta, A.K. +4 more·2010·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2008.03.013PMC PMC3038572

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Abstract

Prior work has demonstrated that the memory dysfunction of Alzheimer's disease (AD) is accompanied by marked cortical pathology in medial temporal lobe (MTL) gray matter. In contrast, changes in white matter (WM) of pathways associated with the MTL have rarely been studied. We used diffusion tensor imaging (DTI) to examine regional patterns of WM tissue changes in individuals with AD. Alterations of diffusion properties with AD were found in several regions including parahippocampal WM, and in regions with direct and secondary connections to the MTL. A portion of the changes measured, including effects in the parahippocampal WM, were independent of gray matter degeneration as measured by hippocampal volume. Examination of regional changes in unique diffusion parameters including anisotropy and axial and radial diffusivity demonstrated distinct zones of alterations, potentially stemming from differences in underlying pathology, with a potential myelin specific pathology in the parahippocampal WM. These results demonstrate that deterioration of neocortical connections to the hippocampal formation results in part from the degeneration of critical MTL and associated fiber pathways.

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Effects of tauopathy on DTI metrics in grey and white matter are complex and may involve axonal damage, myelin injury, neuronal degeneration, and gliosis, which all have been found in tauopathies.
“Effects of tauopathy on DTI metrics in the grey and white matter are complex and may involve axonal damage, myelin injury, neuronal degeneration, and gliosis, which all have been found in tauopathies [17,18,23,25,28,29,33,38,57].”
From Diffusion tensor imaging reveals whole-brain microstructural changes in the P301L mouse model of tauopathy. (2020) · cites this paper as [17]
The Discussion (page unavailable) says the basis of DTI changes is uncertain and identifies possible contributions from axonal and myelin degeneration, oligodendrocyte loss, reactive astrocytosis, and reduced neuropil density in Alzheimer’s disease. The Introduction also describes neuronal loss in Alzheimer’s disease. However, this paper studies DTI changes in white matter; it does not establish the claimed effects on grey-matter DTI metrics or across tauopathies generally. (LLM, conf=0.85)
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“The DA increases reported were widespread, prominently affecting not simply medial temporal lobe tracts such as the fornix and cingulum, but also tracts of temporo-parietal regions such as the superior longitudinal fasciculus [55, 57, 58].”
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Common Alzheimer's Disease Risk Variant Within the CLU Gene Affects White Matter Microstructure in Young Adults
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White matter is altered with parental family history of Alzheimer's disease
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Validation of T 1w‐based segmentations of white matter hyperintensity volumes in large‐scale datasets of aging
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White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease
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Authors: Salat, D. H., Tuch, D. S., van der Kouwe, A. J. W., Greve, D. N., Pappu, V., Lee, S. Y., Hevelone, N. D., Zaleta, A. K., Growdon, J. H., Corkin, S., Fischl, B., & Rosas, H. D.
Affiliations: Massachusetts General Hospital (US)
Corresponding author: Salat, D.H.
ORCID: Salat, D.H.
Greve, D.N.
Hevelone, N.D.
Zaleta, A.K.
Fischl, B.
Rosas, H.D.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2010-02
Volume: 31
Issue: 2
Pages: 244-256
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2008.03.013
PMC: PMC3038572
OpenAlex: W2168247374
Cited by: 279
References: 92
Citations by year: 2026: 2 · 2025: 8 · 2024: 5 · 2023: 10 · 2022: 7 · 2021: 6 · 2020: 13 · 2019: 10 · 2018: 11 · 2017: 14 · 2016: 20 · 2015: 23 · 2014: 17 · 2013: 26 · 2012: 32
FWCI: 17.57
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (F32AG005886, K01AG024898, AG 05886)
National Institute of Nursing Research (R01NR010827)
National Institute of Biomedical Imaging and Bioengineering (U54 EB05149, U54EB005149)
National Center for Research Resources (P41-RR-14075, P41RR014075)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords: Alzheimer's disease, white matter pathology, hippocampal formation, medial temporal lobe, diffusion tensor imaging, fractional anisotropy, axial and radial diffusivity, myelin degeneration, memory impairment, hippocampal volume
MeSH terms: Aged, Alzheimer Disease, Brain, Female, Hippocampus, Humans, Image Processing, Computer-Assisted, Male, Nerve Fibers, Myelinated, Neural Pathways, Organ Size, Anisotropy, Parahippocampal Gyrus, Nerve Fibers, Unmyelinated, Diffusion Tensor Imaging

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