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Aging Neurosci."],"abstract":"<jats:p>In recent years, several studies have suggested that cardiometabolic disorders, such as diabetes, obesity, hypertension, and dyslipidemia, share strong connections with the onset of neurodegenerative disorders such as Parkinson\u2019s and Alzheimer\u2019s disease (AD). However, establishing a definitive link between medical disorders with coincident pathophysiologies is difficult due to etiological heterogeneity and underlying comorbidities. For this reason, amyloid \u03b2 (A\u03b2), a physiological peptide derived from the sequential proteolysis of amyloid precursor protein (APP), serves as a crucial link that bridges the gap between cardiometabolic and neurodegenerative disorders. A\u03b2 normally regulates neuronal synaptic function and repair; however, the intracellular accumulation of A\u03b2 within the brain has been observed to play a critical role in AD pathology. A portion of A\u03b2 is believed to originate from the brain itself and can readily cross the blood-brain barrier, while the rest resides in peripheral tissues that express APP required for A\u03b2 generation such as the liver, pancreas, kidney, spleen, skin, and lungs. Consequently, numerous organs contribute to the body pool of total circulating A\u03b2, which can accumulate in the brain and facilitate neurodegeneration. Although the accumulation of A\u03b2 corresponds with the onset of neurodegenerative disorders, the direct function of periphery born A\u03b2 in AD pathophysiology is currently unknown. This review will highlight the contributions of individual cardiometabolic diseases including cardiovascular disease (CVD), type 2 diabetes (T2D), obesity, and non-alcoholic fatty liver disease (NAFLD) in elevating concentrations of circulating A\u03b2 within the brain, as well as discuss the comorbid association of A\u03b2 with AD pathology.<\/jats:p>","DOI":"10.3389\/fnagi.2021.721858","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T06:49:37Z","timestamp":1629701377000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Cardiometabolic Modification of Amyloid Beta in Alzheimer\u2019s Disease Pathology"],"prefix":"10.3389","volume":"13","author":[{"given":"Marleigh","family":"Hefner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineet","family":"Baliga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailinn","family":"Amphay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Hegde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/nsmb.1799","article-title":"Structural conversion of neurotoxic amyloid-\u03b2(1\u201342) oligomers to fibrils","volume":"17","author":"Ahmed","year":"2010","journal-title":"Nat. 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