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Record W4323657607 · doi:10.1101/2023.03.09.23286881

Altered brain energy metabolism related to astrocytes in Alzheimer’s disease

2023· preprint· en· W4323657607 on OpenAlexaff
Kosei Hirata, Kiwamu Matsuoka, Kenji Tagai, Hironobu Endo, Harutsugu Tatebe, Maiko Ono, Naomi Kokubo, Asaka Oyama, Hitoshi Shinotoh, Keisuke Takahata, Takayuki Obata, Masoumeh Dehghani, Jamie Near, Kazunori Kawamura, Ming‐Rong Zhang, Hitoshi Shimada, Takanori Yokota, Takahiko Tokuda, Makoto Higuchi, Yuhei Takado

Bibliographic record

VenuemedRxiv · 2023
Typepreprint
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsUniversity of TorontoSunnybrook Health Science Centre
FundersJapan Society for the Promotion of ScienceChiba UniversityJikei University School of MedicineJapan Agency for Medical Research and Development
KeywordsInositolInternal medicineGlial fibrillary acidic proteinEndocrinologyAstrocyteAlzheimer's diseaseChemistryBiologyMedicineDiseaseImmunohistochemistryCentral nervous systemReceptor

Abstract

fetched live from OpenAlex

ABSTRACT Objective Increasing evidence suggests that reactive astrocytes are associated with Alzheimer’s disease (AD). However, its underlying pathogenesis remains unknown. Given the role of astrocytes in energy metabolism, reactive astrocytes may contribute to altered energy metabolism. It is hypothesized that lactate, a glucose metabolite, is produced in astrocytes and subsequently shuttled to neurons as an energy substrate. This study aimed to examine alterations in brain lactate levels and their association with astrocytic activities in AD. Methods 30 AD and 30 cognitively unimpaired (CU) subjects were enrolled. For AD subjects, amyloid and tau depositions were confirmed by positron emission tomography using [ 11 C]PiB and [ 18 F]florzolotau, respectively. Lactate and myo-inositol, an astroglial marker, in the posterior cingulate cortex (PCC) were quantified by magnetic resonance spectroscopy (MRS). These MRS metabolites were compared with plasma biomarkers, including glial fibrillary acidic protein (GFAP) as another astrocytic marker. Results Lactate and myo-inositol levels were higher in AD than in CU ( p < 0.05). Lactate levels correlated with myo-inositol levels ( r = 0.272, p = 0.047). Lactate and myo-inositol levels were positively associated with the Clinical Dementia Rating sum-of-boxes scores ( p < 0.05). Significant correlations were noted between myo-inositol levels and plasma GFAP and tau phosphorylated at threonine 181 levels ( p < 0.05). Interpretation We found high lactate levels accompanied by an increased astrocytic marker in the PCC in AD. Thus, impaired lactate shuttle of reactive astrocytes may disrupt energy regulation, resulting in surplus lactate levels. Myo-inositol and plasma GFAP may reflect similar astrocytic changes.

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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.055
GPT teacher head0.345
Teacher spread0.290 · 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

Citations2
Published2023
Admission routes1
Has abstractyes

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