Evidence map›Paper›PMID 40495607›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Presynaptic loss and axonal degeneration synergistically correlate with longitudinal neurodegeneration and cognitive decline.

Dai Shi, Chenghui Ye, Anqi Li, Pan Sun, Guoyu Lan, Laihong Zhang, Xin Zhou, Liemin Zhou, Zhen Liu, Tengfei Guo and 1 more

Abstract read
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In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. A novel eye-tracking digital marker outperforms plasma biomarkers in detecting cognitive impairment.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  5. Ratios of CSF proteins reflect cognitive function in ALS.Alzheimer's research & therapy · 2026
    Article
  6. Review
  7. Article
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

11 authors.

Dai ShiNeurology Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Chenghui YeNeurology Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Anqi LiInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Pan SunInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Guoyu LanInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Laihong ZhangInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Xin ZhouInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Liemin ZhouNeurology Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Zhen LiuInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
Tengfei GuoInstitute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.ORCID 0000-0003-2982-0865
Alzheimer's Disease Neuroimaging Initiative

Funding

Foundation for Distinguished Young Scholars 2023B1515020113Guangdong Basic and Applied Basic ScienceNational Natural Science Foundation of China 82171197National Natural Science Foundation of China 82422027National Natural Science Foundation of China U24A20340Shenzhen Science and Technology Innovation Program RCYX20221008092935096
6 · The paper itself

Abstract

introductionBaseline and longitudinal characteristics of cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) and plasma neurofilament light (NfL) and how they correlate interactively with neurodegeneration and cognitive decline in Alzheimer's disease (AD) are not fully understood.

methodsWe investigated dynamic changes of CSF GAP-43 and plasma NfL across different AD stages and their association with longitudinal neurodegeneration and cognitive decline up to 12 years.

resultsIndividuals with hippocampal atrophy, AD-signature cortical thinning, or hypometabolism (N+) had faster plasma NfL increase rates than healthy individuals, regardless of amyloid/tau status. In contrast, none of these N+ imaging indicators correlated with more rapid increases in CSF GAP-43. Furthermore, CSF GAP-43 and plasma NfL synergistically predicted subsequent gray matter atrophy, cortical thinning, hypometabolism of the middle temporal region, and cognition. DISCUSSION: CSF GAP-43-associated presynaptic loss indicates tau-dependent early neurodegeneration, whereas the axonal degeneration indicated by plasma NfL is a relatively late atrophy/hypometabolism-associated fluid neurodegeneration biomarker. HIGHLIGHTS: Plasma neurofilament light (NfL) was increased in N+ or cognitively impaired individuals. Increases in tau-dependent cerebrospinal fluid CSF growth-associated protein 43 (GAP-43) before imaging neurodegeneration indicators. CSF GAP-43 and plasma NfL are synergistically related to longitudinal neurodegeneration. CSF GAP-43 and plasma NfL are synergistically related to longitudinal cognitive decline.

Indexed as

Alzheimer DiseaseAxonsCognitive DysfunctionGAP-43 ProteinNerve DegenerationNeurofilament ProteinsAgedAged, 80 and overAtrophyBiomarkersFemaleHippocampusHumansLongitudinal StudiesMagnetic Resonance ImagingMaleBiomarkersGAP-43 Proteinneurofilament protein LNeurofilament Proteinstau ProteinsAlzheimer's diseaseaxonal degenerationGAP‐43neurodegenerationNfLpresynaptic loss

Identifiers

PMID40495607
PMCPMC12152369

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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.