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Record W2809901991 · doi:10.1016/j.celrep.2018.06.001

Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections

2018· article· en· W2809901991 on OpenAlexafffund
Taylor W. Schmitz, Marieke Mur, Meghmik Aghourian, Marc‐André Bédard, R. Nathan Spreng

Bibliographic record

VenueCell Reports · 2018
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsUniversité du Québec à MontréalDouglas Mental Health University InstituteMcGill UniversityMontreal Neurological Institute and Hospital
FundersJohnson and Johnson Pharmaceutical Research and DevelopmentNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchGenentechNational Institutes of HealthBristol-Myers SquibbCanada First Research Excellence FundEisaiServierU.S. Department of DefenseEli Lilly and CompanyLundbeckfondenElanBritish AcademyRocheMcGill UniversityDoD Alzheimer's Disease Neuroimaging InitiativePfizerBioClinicaBiogenNovartis Pharmaceuticals CorporationMerckAlzheimer's Drug Discovery FoundationGE HealthcareAlzheimer's Disease Neuroimaging InitiativeJohnson and JohnsonMeso Scale DiagnosticsIXICOTakeda Pharmaceutical CompanyJanssen Alzheimer Immunotherapy Research And DevelopmentAbbVieFujirebio EuropeAlzheimer's Association
KeywordsBasal forebrainCholinergic neuronNeuroscienceCholinergicDegeneration (medical)Basal (medicine)BiologyForebrainAnatomyCentral nervous systemMedicinePathologyEndocrinology

Abstract

fetched live from OpenAlex

The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain's cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer's disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans -synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To further assess whether structural degeneration of these regions in AD reflects cholinergic denervation, we used the [ 18 F] FEOBV radiotracer, which binds to cortico-amygdalar cholinergic terminals. We found that the two BF subregions explain spatially distinct patterns of cortico-amygdalar degeneration, which closely reflect their cholinergic projections, and overlap with [ 18 F] FEOBV indices of cholinergic denervation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.051
GPT teacher head0.339
Teacher spread0.288 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations100
Published2018
Admission routes2
Has abstractyes

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