ArticleNature communications2016
Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer's pathology.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 208 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
208 citing papers in PubMed, 1 synthesis or guideline pooled it, 341 citations in OpenAlex.
- Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade.International journal of molecular sciences · 2022Pooled it
- p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial.Nature medicine · 2024Trial
- Phase 2A Learnings Incorporated into RewinD-LB, a Phase 2B Clinical Trial of Neflamapimod in Dementia with Lewy Bodies.The journal of prevention of Alzheimer's disease · 2024Trial
- Preclinical and randomized clinical evaluation of the p38α kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration.Nature communications · 2022Trial
- The cholinergic system in subtypes of Alzheimer's disease: an in vivo longitudinal MRI study.Alzheimer's research & therapy · 2020Trial
- Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer's Disease: Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial.Journal of Alzheimer's disease : JAD · 2018Trial
- Input-output curves demonstrate motor cortex hyperexcitability associated with cognitive impairment in Alzheimer's disease.Neurobiology of aging · 2026Article
- Article
- Associations between REM sleep EEG slowing and brain cholinergic denervation in aging and Mild Cognitive Impairment.Molecular psychiatry · 2026Article
- Global brain activity links subcortical degeneration to cortical tau progressively across Braak regions over early Alzheimer's disease stages.Nature communications · 2026Article
- APOE4-dependent cholinergic/dopaminergic contributions to clinical symptoms across Alzheimer's disease spectrum: A retrospective observational study.European journal of nuclear medicine and molecular imaging · 2026Article
- Acetylcholine: a candidate substrate for hippocampal predictive learning?Nature reviews. Neuroscience · 2026Review
- Neuroinflammatory and molecular pathways in Alzheimer's disease: mechanistic crosstalk and emerging therapeutic opportunities.Inflammopharmacology · 2026Review
- Path Integration in Alzheimer's Disease: Orientation, Movement, and Theta Rhythmicity.Annual review of neuroscience · 2026Review
- Basal forebrain parvalbumin neuron dysfunction links network oscillation deficits to hippocampal pathology in Alzheimer's disease.Research square · 2026Article
- Dose- and state-dependent enhancement of hippocampal CA1 pyramidal neuron excitability by GM1 ganglioside in male rats with cholinergic lesions.Scientific reports · 2026Article
- TACR3 variant confers resilience to aging and Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- White matter hyperintensities are associated with locus coeruleus atrophy and astrocytic βAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A lifespan staging model of basal forebrain cholinergic vulnerability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Cholinergic Basal Forebrain Atrophy Accelerates Cognitive Decline via Cortical Thinning: The Moderating Role of Amyloid-β Pathology in Preclinical Alzheimer's Disease.Research square · 2026Article
148 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 20 institutions in 4 countries.
Funding
Abstract
There is considerable debate whether Alzheimer's disease (AD) originates in basal forebrain or entorhinal cortex. Here we examined whether longitudinal decreases in basal forebrain and entorhinal cortex grey matter volume were interdependent and sequential. In a large cohort of age-matched older adults ranging from cognitively normal to AD, we demonstrate that basal forebrain volume predicts longitudinal entorhinal degeneration. Models of parallel degeneration or entorhinal origin received negligible support. We then integrated volumetric measures with an amyloid biomarker sensitive to pre-symptomatic AD pathology. Comparison between cognitively matched normal adult subgroups, delineated according to the amyloid biomarker, revealed abnormal degeneration in basal forebrain, but not entorhinal cortex. Abnormal degeneration in both basal forebrain and entorhinal cortex was only observed among prodromal (mildly amnestic) individuals. We provide evidence that basal forebrain pathology precedes and predicts both entorhinal pathology and memory impairment, challenging the widely held belief that AD has a cortical origin.
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Registered trials
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.