Evidence map›Paper›PMID 41944335›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Breakpoints in Alzheimer's disease biomarkers and cognition across the aging spectrum: The Mayo Clinic Study of Aging.

Mingzhao Hu, David S Knopman, Terry Therneau, Angela J Fought, Ekaterina Hofrenning, Val J Lowe, Ronald C Petersen, Alicia Algeciras-Schimnich, Clifford R Jack, Nikki H Stricker and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Mingzhao HuDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
David S KnopmanDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Terry TherneauDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
Angela J FoughtDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
Ekaterina HofrenningDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
Val J LoweDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Alicia Algeciras-SchimnichDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Clifford R JackDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Nikki H StrickerDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.
Michelle M MielkeDepartment of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Prashanthi VemuriDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Jonathan Graff-RadfordDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0003-2770-0691

Funding

SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
Validating the New Criteria for Preclinical Alzheimer's diseaseR01AG041851 · NIA · MAYO CLINIC ROCHESTER · PI JACK, CLIFFORD R., KNOPMAN, DAVID S · 2012 to 2021
$6.3M
Interdisciplinary Infrastructure for Aging Research: Rochester Epidemiology ProjectR33AG058738 · NIA · MAYO CLINIC ROCHESTER · PI LEBRASSEUR, NATHAN K, OLSON, JANET E · 2020 to 2022
$2.4M
"What is N?" Towards operationalizing neurodegeneration in Alzheimer's and related dementiasRF1AG069052 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, MIELKE, MICHELLE M · 2021 to 2021
$2.4M
GHR FoundationNIA NIH HHS P30 AG0062677NIA NIH HHS R01AG041851NIA NIH HHS R01AG058738NIA NIH HHS R33 AG058738NIA NIH HHS RF1 AG069052NIA NIH HHS U01 AG006786
6 · The paper itself

Abstract

introductionWe examined when Alzheimer's disease biomarkers become informative by identifying age-related breakpoints with slope-changing trajectories.

methodsIn 2082 Mayo Clinic Study of Aging participants, we modeled plasma amyloid beta (Aβ)42/40, phosphorylated tau (p-tau)181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid/tau positron emission tomography (PET), hippocampal volume (HVa), and global cognition. Generalized additive models described age trends; Davies' test and piecewise linear regression estimated breakpoints. A C2N subsample (n = 462) provided mass-spectrometry plasma markers (p-tau181, p-tau217, their ratios, Aβ42/40).

resultsIn the full cohort, Aβ42/40, HVa, and cognition declined with age; p-tau181, NfL, GFAP, and amyloid/tau PET increased. We observed single breakpoints (years, 95% CI): GFAP 68.1 (63.5-71.8), NfL 70.7 (65.9-75.6), p-tau181 67.2 (60.3-70.3), amyloid PET 62.3 (56.2-69.3), HVa 68.1 (63.1-71.9), cognition 59.8 (55.4-66.0); tau PET showed none. In the mass-spectrometry subset, p-tau217 and p-tau181 broke at 72.6; their ratios and Aβ42/40 showed no breakpoints. DISCUSSION: Breakpoints cluster near late midlife, suggesting windows for screening and monitoring.

Indexed as

AgingAlzheimer DiseaseCognitionAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersFemaleGlial Fibrillary Acidic ProteinHippocampusHumansMaleMiddle AgedNeurofilament ProteinsPeptide FragmentsPositron-Emission TomographyAmyloid beta-Peptidesamyloid beta-protein (1-42)BiomarkersGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsPeptide Fragmentstau Proteinsage‐related breakpoint thresholdsAlzheimer's diseaseamyloidamyloid/tau positron emission tomographyblood‐based biomarkerglobal cognitionMayo Clinic Study of Agingmild cognitive impairmentneurodegenerationtau

Identifiers

PMID41944335
PMCPMC13054827

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.