Quantitative neurohistological features of frontotemporal degeneration
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Frontotemporal degeneration (FTD) is a neurodegenerative condition that has been principally associated with frontal lobe dementia. In this study, we compared neuropathological abnormalities in frontal, hippocampal, and calcarine cortices from patients assigned a diagnosis of FTD, normal elderly and Alzheimer's disease (AD). Densities of Nissl-stained neurons and lesions which were immunolabeled for tau, beta-amyloid (Abeta), alpha- and beta-synuclein, ubiquitin, glial fibrillary acidic protein (GFAP) and CD68 antigen were determined using computer-assisted, non-biased quantitative microscopy. We found that FTD frontal and hippocampal regions exhibited marked neuron loss, abundant ubiquitin-immunoreactive (ir) dystrophic neurites, GFAP-ir astrocytes, and CD68-ir microglia, while calcarine cortex was spared. No alpha- or beta-synuclein-ir lesions were observed, and neither the density of tau-ir neurofibrillary tangles nor that of Abeta-ir plaques in FTD exceeded normal controls. In addition, there were no neuropathological differences between FTD subjects who presented clinically with a frontal lobe dementia versus an AD-like dementia. These findings indicate that FTD is a category of neurodegnerative dementias with varying clinical presentations that is characterized by the progressive degeneration of select populations of cortical neurons. The molecular neurodegenerative mechanisms that lead to FTD remain to be elucidated.
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In vivo PET and immunohistochemistry studies found increased microglial activation in the frontal and temporal cortices of patients with FTD.
“In vivo PET studies320,321 and immunohistochemistry studies322–324 have found increased microglial activation in the frontal and temporal cortices of patients with FTD.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [324]
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- Authors
- Arnold, S. E., Han, L.-Y., Clark, C. M., Grossman, M., & Trojanowski, J. Q.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Arnold, Steven E.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2000-11
- Volume
- 21
- Issue
- 6
- Pages
- 913-919
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1986349982
- Cited by
- 82
- References
- 31
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 1 · 2014: 4 · 2013: 2 · 2012: 4
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Aging (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG09215, P30AG010124, P01AG009215, AG-10124)
- National Institute of Mental Health (MH-55199, R29MH055199)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- frontotemporal lobar degeneration, frontal lobe dementia, Alzheimer's disease, neuronal loss, astrocytes, microglia, neurofibrillary tangles, amyloid plaques, synuclein, calcarine cortex, neurodegeneration
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Astrocytes, Autopsy, Brain, Dementia, Female, Glial Fibrillary Acidic Protein, Humans, Male, Neurons, Organ Size, Ubiquitins, Neurites, Microglia, Neurodegenerative Diseases, Plaque, Amyloid
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