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pmid:39422361
Decreased Brain pH Correlated With Progression of Alzheimer Disease Neuropathology: A Systematic Review and Meta-Analyses of Postmortem Studies.
Hideo Hagihara · Tsuyoshi Miyakawa
The international journal of neuropsychopharmacology · 2024 doi:10.1093/ijnp/pyae047
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Experiment
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Complete file
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Limited and conflicting studies on brain pH changes, indicative of metabolic alterations associated with neural activity, warrant a comprehensive investigation into their relevance in this neurodegenerative condition. Furthermore, the relationship between these pH changes and established AD neuropathological evaluations, such as Braak staging, remains unexplored.\nMETHODS: We conducted quantitative meta-analyses on postmortem brain and cerebrospinal fluid pH in patients with AD and non-AD controls using publicly available demographic data. We collected raw pH data from studies in the NCBI GEO, PubMed, and Google Scholar databases.\nRESULTS: Our analysis of 20 datasets (723 patient samples and 524 control samples) using a random-effects model showed a significant decrease in brain and cerebrospinal fluid pH in patients compared with controls (Hedges' g = -0.57, P < .0001). This decrease remained significant after considering postmortem interval, age at death, and sex. Notably, pH levels were negatively correlated with Braak stage, indicated by the random-effects model of correlation coefficients from 15 datasets (292 patient samples and 159 control samples) (adjusted r = -0.26, P < .0001). Furthermore, brain pH enhanced the discriminative power of the APOEε4 allele, the most prevalent risk gene for AD, in distinguishing patients from controls in a meta-analysis of 4 combined datasets (95 patient samples and 87 control samples).\nCONCLUSIONS: The significant decrease in brain pH in AD underlines its potential role in disease progression and diagnosis. This decrease, potentially reflecting neural hyperexcitation, could enhance our understanding of neurodegenerative pathology and aid in developing diagnostic strategies.", "claims": [{"id": "claim-method", "statement": "Effect size, measured by Hedges’ g, and standard error were calculated within each dataset, and the random-effects model was applied using the function metagen in the R package meta (version 6.5-0).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39422361", "locator": "sections[6] \"Data Analysis\" paragraph 2", "quote": "Effect size, measured by Hedges’ g, and standard error were calculated within each dataset, and the random-effects model was applied using the function metagen in the R package meta (version 6.5-0)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data analyzed in this study are provided in supplementary Table 2.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39422361", "locator": "sections[8] \"Search Results\" paragraph 2", "quote": "The raw data analyzed in this study are provided in supplementary Table 2."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our analysis of 20 datasets (723 patient samples and 524 control samples) using a random-effects model showed a significant decrease in brain and cerebrospinal fluid pH in patients compared with controls (Hedges’ g = −0.57, P < .0001).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39422361", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We conducted quantitative meta-analyses on postmortem brain and cerebrospinal fluid pH in patients with AD and non-AD controls using publicly available demographic data."}, {"asset": "source:pmid:39422361", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We collected raw pH data from studies in the NCBI GEO, PubMed, and Google Scholar databases."}, {"asset": "source:pmid:39422361", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Our analysis of 20 datasets (723 patient samples and 524 control samples) using a random-effects model showed a significant decrease in brain and cerebrospinal fluid pH in patients compared with controls (Hedges’ g = −0.57, P < .0001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our analysis of 20 datasets (723 patient samples and 524 control samples) using a random-effects model showed a significant decrease in brain and cerebrospinal fluid pH in patients compared with controls (Hedges’ g = −0.57, P < .0001).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:39422361"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE44771", "GSE44770", "GSE44768", "GSE44788", "GSE84422"], "resolved_accessions": ["GSE44771", "GSE44770", "GSE44768", "GSE44788", "GSE84422"], "statements": ["The raw data analyzed in this study are provided in supplementary Table 2."], "basis": "The paper names GSE44771, GSE44770, GSE44768, GSE44788, GSE84422 in NCBI Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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