Decreased Brain pH Correlated With Progression of Alzheimer Disease Neuropathology: A Systematic Review and Meta-Analyses of Postmortem Studies
Abstract Background Altered brain energy metabolism is implicated in Alzheimer disease (AD). 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...
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| Veröffentlicht in: | The international journal of neuropsychopharmacology 2024-10, Vol.27 (10), p.1 |
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| creator | Hagihara, Hideo Miyakawa, Tsuyoshi |
| description | Abstract
Background
Altered brain energy metabolism is implicated in Alzheimer disease (AD). 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.
Methods
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.
Results
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 |
| doi_str_mv | 10.1093/ijnp/pyae047 |
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Background
Altered brain energy metabolism is implicated in Alzheimer disease (AD). 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.
Methods
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.
Results
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).
Conclusions
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.</description><identifier>ISSN: 1461-1457</identifier><identifier>ISSN: 1469-5111</identifier><identifier>EISSN: 1469-5111</identifier><identifier>DOI: 10.1093/ijnp/pyae047</identifier><identifier>PMID: 39422361</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Alzheimer Disease - pathology ; Alzheimer's disease ; Autopsy ; Brain ; Brain - pathology ; Brain Chemistry ; Chemical properties ; Development and progression ; Disease Progression ; Health aspects ; Humans ; Hydrogen-Ion Concentration ; Medical research ; Medicine, Experimental ; Physiological aspects ; Regular</subject><ispartof>The international journal of neuropsychopharmacology, 2024-10, Vol.27 (10), p.1</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of CINP. 2024</rights><rights>The Author(s) 2024. Published by Oxford University Press on behalf of CINP.</rights><rights>COPYRIGHT 2024 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c333t-763f5c0f2873e70ea03bcb871765213836b5e1f4706c9081f248ae6ed46a01473</cites><orcidid>0000-0003-0137-8200 ; 0000-0001-9602-9518</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511658/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511658/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,1605,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39422361$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hagihara, Hideo</creatorcontrib><creatorcontrib>Miyakawa, Tsuyoshi</creatorcontrib><title>Decreased Brain pH Correlated With Progression of Alzheimer Disease Neuropathology: A Systematic Review and Meta-Analyses of Postmortem Studies</title><title>The international journal of neuropsychopharmacology</title><addtitle>Int J Neuropsychopharmacol</addtitle><description>Abstract
Background
Altered brain energy metabolism is implicated in Alzheimer disease (AD). 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.
Methods
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.
Results
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).
Conclusions
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.</description><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer's disease</subject><subject>Autopsy</subject><subject>Brain</subject><subject>Brain - pathology</subject><subject>Brain Chemistry</subject><subject>Chemical properties</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Physiological aspects</subject><subject>Regular</subject><issn>1461-1457</issn><issn>1469-5111</issn><issn>1469-5111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kk1v1DAQhiMEoh9w44wscaAH0npix056QcsWKFKBioI4Wl5nsusqiYPtFIU_wV8mYZeKSgj5YGv8zKOx9SbJE6DHQEt2Yq-7_qQfNVIu7yX7wEWZ5gBw__cZUuC53EsOQrimNOM5Ew-TPVbyLGMC9pOfZ2g86oAVeeW17Uh_TpbOe2x0nGpfbdyQS-_WHkOwriOuJovmxwZti56c2TC3kg84eNfruHGNW4-nZEGuxhCx1dEa8glvLH4nuqvIe4w6XXS6GQOGWXXpQmydn1ByFYfKYniUPKh1E_Dxbj9Mvrx5_Xl5nl58fPtuubhIDWMsplKwOje0zgrJUFLUlK3MqpAgRZ4BK5hY5Qg1l1SYkhZQZ7zQKLDiQlPgkh0mL7fefli1WBnsoteN6r1ttR-V01bdvensRq3djQKYPlfkxWQ42hm8-zZgiKq1wWDT6A7dEBQDkGUpOYcJfbZF17pBZbvaTUoz42pRgOSyEOU80vE_qGlV2FrjOqztVL_T8GLbYLwLwWN9Oz5QNWdDzdlQu2xM-NO_n3wL_wnDBDzfAm7o_6_6BSLuxTA</recordid><startdate>20241001</startdate><enddate>20241001</enddate><creator>Hagihara, Hideo</creator><creator>Miyakawa, Tsuyoshi</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0137-8200</orcidid><orcidid>https://orcid.org/0000-0001-9602-9518</orcidid></search><sort><creationdate>20241001</creationdate><title>Decreased Brain pH Correlated With Progression of Alzheimer Disease Neuropathology: A Systematic Review and Meta-Analyses of Postmortem Studies</title><author>Hagihara, Hideo ; Miyakawa, Tsuyoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c333t-763f5c0f2873e70ea03bcb871765213836b5e1f4706c9081f248ae6ed46a01473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer's disease</topic><topic>Autopsy</topic><topic>Brain</topic><topic>Brain - pathology</topic><topic>Brain Chemistry</topic><topic>Chemical properties</topic><topic>Development and progression</topic><topic>Disease Progression</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Physiological aspects</topic><topic>Regular</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hagihara, Hideo</creatorcontrib><creatorcontrib>Miyakawa, Tsuyoshi</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The international journal of neuropsychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hagihara, Hideo</au><au>Miyakawa, Tsuyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased Brain pH Correlated With Progression of Alzheimer Disease Neuropathology: A Systematic Review and Meta-Analyses of Postmortem Studies</atitle><jtitle>The international journal of neuropsychopharmacology</jtitle><addtitle>Int J Neuropsychopharmacol</addtitle><date>2024-10-01</date><risdate>2024</risdate><volume>27</volume><issue>10</issue><spage>1</spage><pages>1-</pages><issn>1461-1457</issn><issn>1469-5111</issn><eissn>1469-5111</eissn><abstract>Abstract
Background
Altered brain energy metabolism is implicated in Alzheimer disease (AD). 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.
Methods
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.
Results
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).
Conclusions
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.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>39422361</pmid><doi>10.1093/ijnp/pyae047</doi><orcidid>https://orcid.org/0000-0003-0137-8200</orcidid><orcidid>https://orcid.org/0000-0001-9602-9518</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford Journals Open Access Collection; PubMed Central |
| subjects | Alzheimer Disease - pathology Alzheimer's disease Autopsy Brain Brain - pathology Brain Chemistry Chemical properties Development and progression Disease Progression Health aspects Humans Hydrogen-Ion Concentration Medical research Medicine, Experimental Physiological aspects Regular |
| title | Decreased Brain pH Correlated With Progression of Alzheimer Disease Neuropathology: A Systematic Review and Meta-Analyses of Postmortem Studies |
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