Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias

Hussein N. Yassine; Wade Self; Bilal E. Kerman; Giulia Santoni; Nanda Kumar Navalpur Shanmugam; Laila Abdullah; Lesley R. Golden; Alfred N. Fonteh; Michael G. Harrington; Johannes Gräff; Gary E. Gibson; Raj Kalaria; Jose A. Luchsinger; Howard H. Feldman; Russell H. Swerdlow; Lance A. Johnson; Benedict C. Albensi; Berislav V. Zlokovic; Rudolph Tanzi; Stephen Cunnane; Cécilia Samieri; Nikolaos Scarmeas; Gene L. Bowman

doi:10.1002/alz.12845

Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias

Hussein N. Yassine, Wade Self, Bilal E. Kerman, Giulia Santoni, Nanda Kumar Navalpur Shanmugam, Laila Abdullah, Lesley R. Golden, Alfred N. Fonteh, Michael G. Harrington, Johannes Gräff, Gary E. Gibson, Raj Kalaria, Jose A. Luchsinger, Howard H. Feldman, Russell H. Swerdlow, Lance A. Johnson, Benedict C. Albensi, Berislav V. Zlokovic, Rudolph Tanzi, Stephen CunnaneCécilia Samieri, Nikolaos Scarmeas, Gene L. Bowman

Research output: Contribution to journal › Review article › peer-review

12 Scopus citations

Abstract

Disturbances in the brain's capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer's disease (AD) prevention and management. Many diet-derived natural bioactive components can govern cellular energy metabolism but their effects on brain aging are not clear. This review examines how nutritional metabolism can regulate brain bioenergetics and mitigate AD risk. We focus on leading mechanisms of cerebral bioenergetic breakdown in the aging brain at the cellular level, as well as the putative causes and consequences of disturbed bioenergetics, particularly at the blood-brain barrier with implications for nutrient brain delivery and nutritional interventions. Novel therapeutic nutrition approaches including diet patterns are provided, integrating studies of the gut microbiome, neuroimaging, and other biomarkers to guide future personalized nutritional interventions.

Original language	English
Pages (from-to)	1041-1066
Number of pages	26
Journal	Alzheimer's and Dementia
Volume	19
Issue number	3
DOIs	https://doi.org/10.1002/alz.12845
State	Published - Mar 2023

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Funding

We thank Brianna Liu for helping with the figures and Thomas Urich for proofreading the manuscript and assisting with the references. H.N.Y. is supported by R13AG069386, R21AG056518, R01AG055770, R01AG054434, R01AG067063, RF1AG076124 and RF1AG078362 from the National Institute on Aging as well as Alzheimer’ Association and receives consulting fees from Huron Consulting Firm. H.N.Y. was the NMD PIA co‐chair 2019‐2021, and sits on the ISTAART Advisory board 2022–2024. G.G. is supported by 2P01AG014930‐15A1, R01AG043679 from Alzheimer's Drug Discovery Foundation as well as Method for treating neurodegenerating diseases with benfotiamine or derivatives thereof for Patents planned, issued or pending. M.G.H. is supported by 1R01AG054434, 2P01AG052350‐06, RO1AG063857, RO1 AG055770 from L.K. Whittier Foundation and W.M. Keck Foundation as well as R01NS072497 for grants or contracts. M.G.H. is also a member of NINDS Study Section ZRG1 BDCN‐W, NINDS Headache CDE Working Group, Co‐Chair of Biomarkers Committee. R.S. is supported by P30072973 from the National Institute on Aging as well as honoraria for lectures from Nestle Health. S.C. receives funding from Nestlé Health Science SC: Payment to institution—Abitec SC: Research materials. S.C. has License for BrainXpert product. S.C.: Paid to me and institution. S.C. receives consulting fees from Nestlé Health Science, Cargill and Abbott. S.C. receives payment or honoraria from Nestlé Health Science SC: Paid to me. S.C. receives support for attending meetings and/or travel from Nestlé Health Science. S.C. has Patents planned, issued or pending from MCT formulation, co‐inventor with Bernard Cuenoud, Nestlé Health Science. S.C. has participation on a Data Safety Monitoring Board or Advisory Board from AB—Nestlé Health Science, AB—Abbott, AB—Cargill SC: Paid to me, and receives equipment, materials, drugs, medical writing, gifts or other services from Abitec, research materials SC: Institution. N.S. receives funding from EISAI—Local Pi of recruiting site for multinational, multicenter industry sponsored phase III treatment trial for Alzheimer's disease NS: Payments to Institution, and EPAD—Local PI of recruiting site for multinational, multicenter Innovative Medicines Initiative (IMI) sponsored observational study of prodromal stages of dementia NS: Payments to Institution, as well as NovoNordisc—Local PI of recruiting site for multinational, multicenter industry sponsored phase III treatment trial for Alzheimer's disease NS: Payments to Institution. N.S. chairs and receives funding from the Albert Einstein College of Medicine Data Safety Monitoring Board‐ NIH funded study NS. J.G. receives funding from ERC Starting Grant, StG 678832 as well as patents planned, issued or pending on Inventor for European Patent No. 16180434.9 “Methods of Diagnosis Alzheimer's Disease.” Co‐Inventor for U.S. patent 12/917,402 “The Use of CI‐994 and Dinaline for the Treatment of Memory/Cognition and Anxiety Disorders.” L.A.J. is supported by R01 AG062550, R01 AG060056 from the National Institute on Aging as well as Cure Alzheimer's Fund. J.L. is supported by Springer for co‐editor of the book Diabetes and the Brain. J.L. also receives consulting fees from vTv therapeutics. H.F. receives funding from Annovis (QR Pharma), Vivoryon (Probiodrug), AC immune, and LuMind; service agreements for consulting activities with Genetech (DSMB), Roche/Banner (DMC), Tau Consortium (SAB), Samus Theraputics, Biosplice Therapeutics, Axon Neurosciences, Novo Nordisk Inc., Janssen Research & Development LLC; and travel funding from World Events Forum (ADDF) with no personal funds received and all payments to UCSD. HF also reports a philanthropic donation from the Epstein Family Alzheimer's Disease Collaboration for therapeutic research in AD. G.L.B. is supported by R01 AG043398 from NIH/NIA as well as R90AT008924 from NIH/NCCIH. G.L.B. is a founder 2015, served as co‐chair 2015–2019 and immediate past co‐chair 2019–2021. H.Y., G.L.B., B.A., C.S., and W.S. are all members of the NMD PIA, ISTAART.

Funders	Funder number
Albert Einstein College of Medicine Data Safety Monitoring Board‐ NIH
Biosplice Therapeutics
EPAD
NovoNordisc
Samus Theraputics
World Events Forum
National Institutes of Health (NIH)
National Institute on Aging	2P01AG014930‐15A1, R90AT008924, R01AG043679
National Institute on Aging
W. M. Keck Foundation	P30072973, R01NS072497
W. M. Keck Foundation
Alzheimer's Drug Discovery Foundation	RO1AG063857, 2P01AG052350‐06, RO1 AG055770, 1R01AG054434, R01 AG043398
Alzheimer's Drug Discovery Foundation
Cure Alzheimer's Fund
National Center for Complementary and Integrative Health
Rainwater Tau Consortium
Engineering Research Centers	R01 AG062550, 678832, R01 AG060056, 16180434.9
Engineering Research Centers
Eisai
Novo Nordisk A/S
Sächsische Aufbaubank
Innovative Medicines Initiative
multicenter Innovative Medicines Initiative

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/alz.12845

Cite this

Yassine, H. N., Self, W., Kerman, B. E., Santoni, G., Navalpur Shanmugam, N. K., Abdullah, L., Golden, L. R., Fonteh, A. N., Harrington, M. G., Gräff, J., Gibson, G. E., Kalaria, R., Luchsinger, J. A., Feldman, H. H., Swerdlow, R. H., Johnson, L. A., Albensi, B. C., Zlokovic, B. V., Tanzi, R., ... Bowman, G. L. (2023). Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias. Alzheimer's and Dementia, 19(3), 1041-1066. https://doi.org/10.1002/alz.12845

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title = "Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias",

abstract = "Disturbances in the brain's capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer's disease (AD) prevention and management. Many diet-derived natural bioactive components can govern cellular energy metabolism but their effects on brain aging are not clear. This review examines how nutritional metabolism can regulate brain bioenergetics and mitigate AD risk. We focus on leading mechanisms of cerebral bioenergetic breakdown in the aging brain at the cellular level, as well as the putative causes and consequences of disturbed bioenergetics, particularly at the blood-brain barrier with implications for nutrient brain delivery and nutritional interventions. Novel therapeutic nutrition approaches including diet patterns are provided, integrating studies of the gut microbiome, neuroimaging, and other biomarkers to guide future personalized nutritional interventions.",

author = "Yassine, {Hussein N.} and Wade Self and Kerman, {Bilal E.} and Giulia Santoni and {Navalpur Shanmugam}, {Nanda Kumar} and Laila Abdullah and Golden, {Lesley R.} and Fonteh, {Alfred N.} and Harrington, {Michael G.} and Johannes Gr{\"a}ff and Gibson, {Gary E.} and Raj Kalaria and Luchsinger, {Jose A.} and Feldman, {Howard H.} and Swerdlow, {Russell H.} and Johnson, {Lance A.} and Albensi, {Benedict C.} and Zlokovic, {Berislav V.} and Rudolph Tanzi and Stephen Cunnane and C{\'e}cilia Samieri and Nikolaos Scarmeas and Bowman, {Gene L.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2023",

month = mar,

doi = "10.1002/alz.12845",

language = "English",

volume = "19",

pages = "1041--1066",

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Yassine, HN, Self, W, Kerman, BE, Santoni, G, Navalpur Shanmugam, NK, Abdullah, L, Golden, LR, Fonteh, AN, Harrington, MG, Gräff, J, Gibson, GE, Kalaria, R, Luchsinger, JA, Feldman, HH, Swerdlow, RH, Johnson, LA, Albensi, BC, Zlokovic, BV, Tanzi, R, Cunnane, S, Samieri, C, Scarmeas, N & Bowman, GL 2023, 'Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias', Alzheimer's and Dementia, vol. 19, no. 3, pp. 1041-1066. https://doi.org/10.1002/alz.12845

TY - JOUR

T1 - Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias

AU - Yassine, Hussein N.

AU - Self, Wade

AU - Kerman, Bilal E.

AU - Santoni, Giulia

AU - Navalpur Shanmugam, Nanda Kumar

AU - Abdullah, Laila

AU - Golden, Lesley R.

AU - Fonteh, Alfred N.

AU - Harrington, Michael G.

AU - Gräff, Johannes

AU - Gibson, Gary E.

AU - Kalaria, Raj

AU - Luchsinger, Jose A.

AU - Feldman, Howard H.

AU - Swerdlow, Russell H.

AU - Johnson, Lance A.

AU - Albensi, Benedict C.

AU - Zlokovic, Berislav V.

AU - Tanzi, Rudolph

AU - Cunnane, Stephen

AU - Samieri, Cécilia

AU - Scarmeas, Nikolaos

AU - Bowman, Gene L.

PY - 2023/3

Y1 - 2023/3

N2 - Disturbances in the brain's capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer's disease (AD) prevention and management. Many diet-derived natural bioactive components can govern cellular energy metabolism but their effects on brain aging are not clear. This review examines how nutritional metabolism can regulate brain bioenergetics and mitigate AD risk. We focus on leading mechanisms of cerebral bioenergetic breakdown in the aging brain at the cellular level, as well as the putative causes and consequences of disturbed bioenergetics, particularly at the blood-brain barrier with implications for nutrient brain delivery and nutritional interventions. Novel therapeutic nutrition approaches including diet patterns are provided, integrating studies of the gut microbiome, neuroimaging, and other biomarkers to guide future personalized nutritional interventions.

AB - Disturbances in the brain's capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer's disease (AD) prevention and management. Many diet-derived natural bioactive components can govern cellular energy metabolism but their effects on brain aging are not clear. This review examines how nutritional metabolism can regulate brain bioenergetics and mitigate AD risk. We focus on leading mechanisms of cerebral bioenergetic breakdown in the aging brain at the cellular level, as well as the putative causes and consequences of disturbed bioenergetics, particularly at the blood-brain barrier with implications for nutrient brain delivery and nutritional interventions. Novel therapeutic nutrition approaches including diet patterns are provided, integrating studies of the gut microbiome, neuroimaging, and other biomarkers to guide future personalized nutritional interventions.

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Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

Access to Document

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