Biomarkers in frontotemporal lobar degenerations—Progress and challenges

Hu, William T.; Trojanowski, John Q.; Shaw, Leslie M.

doi:10.1016/j.pneurobio.2011.04.012

Cited by 42Dementia and Cognitive Impairment ResearchAmyotrophic Lateral Sclerosis ResearchAlzheimer's disease research and treatments

Biomarkers in frontotemporal lobar degenerations—Progress and challenges

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Hu, William T., Trojanowski, John Q., Shaw, Leslie M.·2011·Progress in Neurobiology

DOI 10.1016/j.pneurobio.2011.04.012PMC PMC3173583

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Abstract

Neuronal and glial changes associated with tau, TAR DNA binding protein of ∼43 kDa (TDP-43), and fused in sarcoma (FUS) together constitute the pathologic spectrum of frontotemporal lobar degeneration (FTLD). Most patients with FTLD present with prominent behavior or language changes, sometimes accompanied by extrapyramidal symptoms or motor neuron disease. Identification of FTLD patients with mutations in genes for tau, TDP-43, and FUS lends strong support for their pathogenic roles in FTLD, and elucidation of their dysfunction will pave the way for development of substrate specific therapy. However, there remains no reliable biomarker for early detection of FTLD or prediction of underlying FTLD pathologic change. Clinical syndromes usually reflects the earliest affected brain regions where atrophy can be visualized on structural MRI, but neither clinical nor structural imaging-based biomarkers has been accurately correlated with underlying pathology on the individual patient level. Biochemical markers in the cerebrospinal fluid (CSF) have also been investigated in FTLD and related disorders, including amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP). However, their accuracy and pathologic significance need to be confirmed in future multi-center studies. Here we review the progress made in FTLD biomarkers, including clinical phenotype/feature characterization, neuropsychological analysis, CSF and plasma analytes, and patterns of brain atrophy and network dysfunction detectable on brain imaging. Given the pathologic overlap of FTLD with ALS and PSP, collaboration with specialists in those fields will be essential in the translation of promising FTLD biomarkers into clinical practice.

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Extracellular tau is not a primary target in non-AD tauopathies.
“CSF tau levels are not increased in non-AD tauopathies57–60, suggesting that extracellular tau is not a primary target in these conditions.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [58]
CSF tau levels are not increased in non-AD tauopathies.
“CSF tau levels are not increased in non-AD tauopathies57–60, suggesting that extracellular tau is not a primary target in these conditions.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [58]

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Petersen RC Aisen PS Beckett LA Donohue MC Gamst AC Harvey DJ Jack CR Jr. Jagust WJ Shaw LM Toga AW Trojanowski JQ Weiner MW Alzheimer’s Disease Neuroimaging Initiative (ADNI): clinical characterization Neurology 2010 74 201 209 20042704 PMC2809036

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Authors: Hu, W. T., Trojanowski, J. Q., & Shaw, L. M.
Affiliations: Emory University (US)
University of Pennsylvania (US)
Corresponding author: Hu, William T.
ORCID: Hu, William T.
Trojanowski, John Q.
Shaw, Leslie M.
Venue: Progress in Neurobiology
Publisher: Elsevier BV
Published: 2011-12
Volume: 95
Issue: 4
Pages: 636-648
ISSN: 0301-0082 (ISSN-L)
DOI: 10.1016/j.pneurobio.2011.04.012
PMC: PMC3173583
OpenAlex: W2032404852
Cited by: 42
References: 162
Citations by year: 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 8
FWCI: 0.88
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neurobiology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (P30AG010124, P01AG017586, AG17586, AG-10124)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords: frontotemporal lobar degeneration, biomarkers, tau protein, TDP-43, FUS, cerebrospinal fluid biomarkers, plasma biomarkers, brain atrophy, network dysfunction, amyotrophic lateral sclerosis, progressive supranuclear palsy, early detection, neuropsychological assessment, clinical phenotype
MeSH terms: Amyotrophic Lateral Sclerosis, DNA-Binding Proteins, Humans, Mutation, Supranuclear Palsy, Progressive, Biomarkers, tau Proteins, Disease Progression, RNA-Binding Protein FUS, Frontotemporal Lobar Degeneration, Neuroimaging

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Biomarkers in frontotemporal lobar degenerations—Progress and challenges

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