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A decline in glucose metabolism is a common feature across a number of neurodegenerative diseases. Another common feature is the progressive accumulation of insoluble protein deposits, it\u2019s unclear if the two are linked. Glucose metabolism in the brain is highly coupled between neurons and glia, with glucose taken up by glia and metabolised to lactate, which is then shuttled via transporters to neurons, where it is converted back to pyruvate and fed into the TCA cycle for ATP production. Monocarboxylates are also involved in signalling, and play broad ranging roles in brain homeostasis and metabolic reprogramming. However, the role of monocarboxylates in dementia has not been tested. Here, we find that increasing pyruvate import in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    neurons by over-expression of the transporter\n                    <jats:italic>bumpel<\/jats:italic>\n                    , leads to a rescue of lifespan and behavioural phenotypes in fly models of both frontotemporal dementia and Alzheimer\u2019s disease. The rescue is linked to a clearance of late stage autolysosomes, leading to degradation of toxic peptides associated with disease. We propose upregulation of pyruvate import into neurons as potentially a broad-scope therapeutic approach to increase neuronal autophagy, which could be beneficial for multiple dementias.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1010893","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T13:22:35Z","timestamp":1695302555000},"page":"e1010893","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["A monocarboxylate transporter rescues frontotemporal dementia and Alzheimer\u2019s disease models"],"prefix":"10.1371","volume":"19","author":[{"given":"Dongwei","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9441-2211","authenticated-orcid":true,"given":"Andr\u00e9s","family":"Gonz\u00e1lez-Guti\u00e9rrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Aleyakpo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharifah","family":"Anoar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8470-7908","authenticated-orcid":true,"given":"Ashling","family":"Giblin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3819-2023","authenticated-orcid":true,"given":"Magda L.","family":"Atilano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunxin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9722-7399","authenticated-orcid":true,"given":"Annora","family":"Thoeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elli","family":"Tsintzas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9073-1088","authenticated-orcid":true,"given":"Marie","family":"Maeland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian M.","family":"Isaacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-146X","authenticated-orcid":true,"given":"Jimena","family":"Sierralta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9337-0411","authenticated-orcid":true,"given":"Teresa","family":"Niccoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"issue":"10","key":"pgen.1010893.ref001","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.tins.2013.07.001","article-title":"Sugar for the brain: the role of glucose in physiological and pathological brain function","volume":"36","author":"P Mergenthaler","year":"2013","journal-title":"Trends in neurosciences"},{"issue":"5","key":"pgen.1010893.ref002","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.neuron.2012.08.019","article-title":"Synaptic energy use and supply","volume":"75","author":"JJ Harris","year":"2012","journal-title":"Neuron"},{"issue":"4","key":"pgen.1010893.ref003","doi-asserted-by":"crossref","first-page":"e1002987","DOI":"10.1371\/journal.pcbi.1002987","article-title":"Generative FDG-PET and MRI model of aging and disease progression in Alzheimer\u2019s disease","volume":"9","author":"J Dukart","year":"2013","journal-title":"PLoS computational biology"},{"issue":"46","key":"pgen.1010893.ref004","first-page":"16265","article-title":"Region-specific hierarchy between atrophy, hypometabolism, and beta-amyloid (Abeta) load in Alzheimer\u2019s disease dementia. 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