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Record W4416409411 · doi:10.1016/j.jad.2025.120721

The effects of Lithium on Beta-amyloid deposition and tau phosphorylation: A systematic review

2025· article· en· W4416409411 on OpenAlexaff
Kelei Xiao, Hisham Sayed, Jingwen Ai, Elizaveta Kirichek, Gia Han Le, Sabrina Wong, Kyle Valentino, Kayla M. Teopiz, Maj Vinberg, Joshua D. Rosenblat, Heidi Ka Ying Lo, Melanie C. Zhang, Roger S. McIntyre

Bibliographic record

VenueJournal of Affective Disorders · 2025
Typearticle
Languageen
FieldMedicine
TopicBipolar Disorder and Treatment
Canadian institutionsUniversity Health NetworkBrain and Cognition Discovery FoundationUniversity of TorontoMcMaster University
Fundersnot available
KeywordsLithium (medication)Deposition (geology)Amyloid βReplicatePhosphorylationAnimal modelAmyloid (mycology)

Abstract

fetched live from OpenAlex

Current anti-amyloid treatments often cause amyloid-related imaging abnormalities in the treatment of Alzheimer's disease (AD). Lithium demonstrates neuroprotective and neurotrophic effects, and preclinical studies indicate it reduces intracerebral amyloid deposition and tau phosphorylation. This systematic review evaluates lithium's effects on beta-amyloid, tau, and cognitive deficits in major neurocognitive disorders. A systematic review of primary research was conducted using Embase, PsycInfo, MEDLINE, and PubMed databases from inception to September 2024, following PRISMA criteria. Animal and adult human studies evaluating lithium monotherapy's effects on AD were included. Long-term low-dose lithium treatment demonstrates inconsistent efficacy in lowering intracerebral amyloid deposition and reversing AD-related cognitive deficits in preclinical and clinical trials. Lithium potentially slows amyloid plaque formation in pre-plaque stages through increasing heat shock proteins and suppressing protein synthesis in preclinical trials. Intracerebral lithium concentrations above 1 mM reduced phosphorylated tau through promoting tau ubiquitination and inhibiting CDK5 signalling in preclinical trials. AD currently needs a comprehensive animal model accurately representing human AD symptoms and progression, and more clinical trials are needed. Several included studies utilize peripheral lithium administration, which complicates assessment of effective intracerebral concentrations. Lithium potentially reduces intracerebral amyloid deposition and tau phosphorylation in AD animal models and may reverse associated cognitive deficits. Further research should seek to replicate similar findings in larger samples and explore lithium's optimal dosage range in promoting intracerebral amyloid clearance. • Lithium may decrease intracerebral Aβ42 levels 4.5 fold • Lithium may reduce amyloid plaque count and size by 45–54.9 % post-plaque formation • Lithium may reverse cognitive deficits in adults with major neurocognitive disorders • Lithium may reduce tau phosphorylation by 50–60 %

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)0.003
metaresearch head score (Gemma)0.009
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Systematic review · Consensus signal: Systematic review
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.008
Threshold uncertainty score0.020

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.009
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0070.006
Bibliometrics0.0060.007
Science and technology studies0.0000.000
Scholarly communication0.0020.001
Open science0.0020.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0060.000

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 head0.004
GPT teacher head0.255
Teacher spread0.252 · 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 designSystematic review
Domainnot available
GenreReview

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

Citations1
Published2025
Admission routes1
Has abstractyes

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