Evidence map›Paper›PMID 41293128›Full record

ReviewFrontiers in molecular neuroscience2025

The transcriptional and cellular landscape of cognitive resilience to Alzheimer's disease.

Nina Khera, Ravikiran M Raju, Stuart A Lipton

Abstract readReview
In one paragraph

Review in Frontiers in molecular neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

3 authors.

Nina KheraHarvard College, Cambridge, MA, United States.
Ravikiran M RajuPicower Institute of Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, United States.
Stuart A LiptonDepartment of Molecular & Cellular Biology, Neurodegeneration New Medicines Center, The Scripps Research Institute, La Jolla, CA, United States.

Funding

Novel Proteomics Approach to HIV-Associated Neurocognitive Disorder & Drug AbuseDP1DA041722 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2016 to 2020
$7.0M
Leadership in AD/ADRD Drug DiscoveryR35AG071734 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2021 to 2025
$5.4M
Dynamic Interactions of the S-Nitrosoproteome in Type 2 Diabetes/Metabolic Syndrome and Alzheimer’s DiseaseRF1AG057409 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2020
$4.1M
S-Nitrosylation-Induced Posttranslational Modification and Aberrant Cell Signaling in Sporadic Alzheimer's DiseaseR01AG056259 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2017 to 2021
$3.3M
Aberrant protein S-nitrosylation mediates Gene-Environment Interactions in AD/ADRDU01AG088679 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI STUART A LIPTON, Tomohiro Nakamura · 2024 to 2026
$2.7M
Crosstalk between innate-immunity human microglia and adaptive-immunity Tregs in Alzheimer's diseaseR01AG078756 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI STUART A LIPTON · 2022 to 2026
$2.3M
Pro-Electrophilic Drugs PEDs for Alzheimer's DiseaseR56AG065372 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LIPTON, STUART A · 2020 to 2021
$1.8M
Elucidating the neuronal mechanisms underlying cognitive resilience to Alzheimer's DiseaseK08AG086586 · NIA · BOSTON CHILDREN'S HOSPITAL · PI Ravikiran M Raju · 2025 to 2026
$336k
NIA NIH HHS K08 AG086586NIA NIH HHS R01 AG056259NIA NIH HHS R01 AG078756NIA NIH HHS R35 AG071734NIA NIH HHS R56 AG065372NIA NIH HHS RF1 AG057409NIA NIH HHS U01 AG088679NIDA NIH HHS DP1 DA041722
6 · The paper itself

Abstract

It is estimated that 5%-40% of patients with pathological features of Alzheimer's disease (AD) maintain normal cognitive health throughout their lifetimes, a phenomenon known as cognitive resilience. Studies have identified many factors that contribute to a patient's capacity for resilience, with those that modulate gene expression being the most dynamic, adaptable, and potentially addressable as targets for future drug development. In patients cognitively resilient to AD and AD-related dementias (ADRD), transcriptional changes within specific cell types serve to preserve the processes most critical to cognitive function within each cell, exerting protective effects on other cell types as well via non-cell autonomous effects. Key themes in preserved cognitive function include maintenance of synaptic stability and function, dampening neuronal hyperexcitability, reducing misfolded protein accumulation, increasing myelination, and countering neuroinflammation. With future research on the most upstream and impactful transcriptional drivers, there lies immense potential for both therapeutics to address AD and a greater fundamental understanding of AD and the brain.

Indexed as

Alzheimer’s diseasecognitive resilienceMEF2CNrf2REST (RE-1 silencing transcription factor)transcription factor

Identifiers

PMID41293128
PMCPMC12640947

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.