Tau Beats Amyloid in Predicting Brain Atrophy in Alzheimer Disease: Implications for Prognosis and Clinical Trials
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Several biomarkers have emerged in the past few decades to quantify pathologic brain changes related to Alzheimer disease (AD). In particular, PET radiotracers that bind selectively to amyloid-β plaques and tau neurofibrillary tangles have advanced AD research and drug development by enabling the
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Amyloid pathology typically develops first followed by tau pathology, which correlates with AD progression and cognitive impairment.
“Amyloid pathology typically develops first followed by tau pathology, which correlates with AD progression and cognitive impairment2–4.”
From The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway (2025) · cites this paper as [2]
The paper’s discussion of amyloid and tau PET (page not provided) describes early amyloid accumulation and tau spreading in the presence of amyloid, but does not establish that amyloid pathology typically begins before tau pathology. It does state that increasing tau spread is associated with clinical impairment and that tau tangles are strongly associated with cognitive deficits. (LLM, conf=0.83)
Experimental — accuracy not yet measuredAmyloid pathology typically develops early in AD whereas tau pathology occurs later but correlates more accurately with AD progression and cognitive impairment.
“Amyloid pathology typically develops early in AD whereas tau pathology occurs later but correlates more accurately with AD progression and cognitive impairment3–5.”
From <i>APOE3</i> - <i>R136S</i> mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition (2024) · cites this paper as [3]
In the F-flutametamol section (page unavailable), the paper says amyloid PET retention begins about two decades before symptoms and reports that tau is more closely associated than amyloid with neurodegeneration and cognitive impairment. It describes tau spreading through the cortex in the presence of amyloid, but does not establish that tau pathology itself first occurs later than amyloid pathology. (LLM, conf=0.83)
Experimental — accuracy not yet measured
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Cites
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“Increasing spread of tau is associated with clinical impairment (10–12), with the tau PET binding topography associated with domain-specific cognitive deficits (13,14) and distinct AD clinical variants (9,15,16), The relationships between amyloid and tau PET and clinical measures largely replicate clinicopathologic st…”
BackgroundDonanemab in Early Alzheimer’s Disease
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“In a recent phase 2 trial of donanemab (37), a monoclonal antibody targeting the pyroglutamate epitope on Ab plaques, (18)F-flortaucipir PET was used to limit trial inclusion to patients with intermediate tau deposition.”
MethodPET Imaging of Tau Deposition in the Aging Human Brain
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“In head-to-head comparisons, tau PET binding in temporoparietal regions outperformed amyloid PET and structural MRI measures in predicting cognitive decline (26–28), especially in patients at early AD stages (26).”
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Comorbid neuropathological diagnoses in early versus late-onset Alzheimer's disease
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- Authors
- Malpetti, M., Joie, R. L., & Rabinovici, G. D.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2022-06
- Volume
- 63
- Issue
- 6
- Pages
- 830-832
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- PMC
- PMC9157718
- OpenAlex
- W4281663419
- Cited by
- 45
- References
- 10
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 10 · 2023: 4
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Medical Research Council (MR/L023784/2, MR/M008983/1, MR/T033371/1, MC_UU_00030/14)
- 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 › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- tau PET, amyloid PET, brain atrophy, Alzheimer's disease, neurodegeneration biomarkers, neurofibrillary tangles, amyloid plaques, prognosis, clinical trial endpoints
- MeSH terms
- Alzheimer Disease, Amyloid, Amyloidosis, Atrophy, Brain, Clinical Trials as Topic, Humans, Prognosis, Amyloidogenic Proteins
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