{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:46:42Z","timestamp":1790704002367,"version":"4.1.0"},"reference-count":132,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Aging","award":["1RF1AG058603"],"award-info":[{"award-number":["1RF1AG058603"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD), an age-related neurodegenerative disorder, is currently incurable. Imbalanced amyloid-beta (A\u03b2) generation and clearance are thought to play a pivotal role in the pathogenesis of AD. Historically, strategies targeting A\u03b2 clearance have typically focused on central clearance, but with limited clinical success. Recently, the contribution of peripheral systems, particularly the liver, to A\u03b2 clearance has sparked an increased interest. In addition, AD presents pathological features similar to those of metabolic syndrome, and the critical involvement of brain energy metabolic disturbances in this disease has been recognized. More importantly, the liver may be a key regulator in these abnormalities, far beyond our past understanding. Here, we review recent animal and clinical findings indicating that liver dysfunction represents an early event in AD pathophysiology. We further propose that compromised peripheral A\u03b2 clearance by the liver and aberrant hepatic physiological processes may contribute to AD neurodegeneration. The role of a hepatic synthesis product, fibroblast growth factor 21 (FGF21), in the management of AD is also discussed. A deeper understanding of the communication between the liver and brain may lead to new opportunities for the early diagnosis and treatment of AD.<\/jats:p>","DOI":"10.3390\/nu14204298","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T03:43:58Z","timestamp":1665978238000},"page":"4298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Targeting Alzheimer\u2019s Disease: The Critical Crosstalk between the Liver and Brain"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhihai","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung Wen (Kevin)","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-1664","authenticated-orcid":false,"given":"Xuemei","family":"Zong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5541","DOI":"10.2147\/IJN.S200490","article-title":"Alzheimer\u2019s disease: Pathogenesis, diagnostics, and therapeutics","volume":"14","author":"Tiwari","year":"2019","journal-title":"Int. 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