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Cited by 35Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Tau and Alzheimer's disease: Past, present and future

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Iqbal, Khalid·2024·Cytoskeleton
DOI 10.1002/cm.21822PMC PMC10977900
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Abstract

My journey with tau started when in 1974 for the first time I isolated neurofibrillary tangles of paired helical filaments (PHFs) from autopsied Alzheimer's disease (AD) brains and discovered that they were made up of a ~50–70 KDa protein on SDS‐polyacrylamide gels. Subsequently my team discovered that this PHF protein and the microtubule‐associated factor called tau were one and the same protein. However, we found that tau in neurofibrillary tangles/PHFs in AD brain was abnormally hyperphosphorylated, and unlike normal tau, which promoted the assembly of tubulin into microtubules, the AD‐hyperphosphorylated tau inhibited microtubule assembly. These discoveries of tau pathology in AD opened a new and a major area of research on tau and on the molecular pathology of this major cause of dementia in middle‐ and old‐age individuals. Tau pathology, which without fail is made up of the aggregated hyperphosphorylated state of the protein, is also the hallmark lesion of a family of around 20 related neurodegenerative diseases, called tauopathies. Currently, tau pathology is a major drug target for the treatment of AD and related tauopathies. Both active and passive tau immunization human clinical trials at various stages are underway. Initial results range from negative to partially promising. Future studies will reveal whether tau therapy alone or in combination with drugs targeting Aβ and/or neurodegeneration will be required to achieve the most effective treatment for AD and related disorders.

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Cited by

Sorted by citations

Authors
Iqbal, K.
Affiliations
Fujirebio US (United States) (US)
Corresponding author
Iqbal, Khalid
ORCID
Iqbal, Khalid
Venue
Cytoskeleton
Publisher
Wiley
Published
2023-12-21
Volume
81
Issue
1
Pages
116-121
ISSN
  • 1949-3584 (ISSN-L)
  • 1949-3592
DOI
10.1002/cm.21822
PMC
PMC10977900
OpenAlex
W4390051461
Cited by
35
References
8
Citations by year
2026: 13 · 2025: 17 · 2024: 5
FWCI
1.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Cytoskeleton (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (AG079671)
  • Office for People With Developmental Disabilities
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
tau protein, Alzheimer's disease, tauopathy, neurofibrillary tangles, paired helical filaments, tau hyperphosphorylation, microtubule assembly, tau immunotherapy, amyloid-beta, dementia
MeSH terms
Alzheimer Disease, Humans, Microtubules, Neurofibrillary Tangles, tau Proteins, Tauopathies

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