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Levels of pro-inflammatory cytokines and AD pathological biomarkers was measured by ELISA and Simoa Technology, respectively. 9 monkeys evaluated ex vivo for AD-like pathology (<jats:italic>n<\/jats:italic>\u2009=\u20096 \/ T2DM group, age 22.17, FPG\u2009\u2265\u2009126\u00a0mg\/dL, and <jats:italic>n<\/jats:italic>\u2009=\u20093 \/ NC group, age 14.67, FPG\u2009&lt;\u2009100\u00a0mg\/dL). To evaluate the pathological features of AD in the brains of T2DM monkeys, we assessed the levels of A\u03b2, phospho-tau, and neuroinflammation using immunohistochemistry, which further confirmed the deposition of A\u03b2 plaques by Bielschowsky\u2019s silver, Congo red, and Thioflavin S staining. Synaptic damage and neurodegeneration were assessed by immunofluorescence.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found not only increased levels of pro-inflammatory cytokines such as tumor necrosis factor-\u03b1 (TNF-\u03b1) in peripheral blood (PB) and brain of T2DM monkeys but also changes in PB of AD pathological biomarkers such as decreased \u03b2-amyloid (A\u03b2) 42 and A\u03b240 levels. Most notably, we observed AD-like pathological features in the brain of T2DM monkeys, including A\u03b2 plaque deposition, p-tau from neuropil thread to pre-neurofibrillary tangles (NFTs), and even the appearance of extracellular NFT. Microglia were activated from a resting state to an amoeboid. Astrocytes showed marked hypertrophy and an increased number of cell bodies and protrusions. Finally, we observed impairment of the postsynaptic membrane but no neurodegeneration or neuronal death.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Overall, T2DM monkeys showed elevated levels of peripheral and intracerebral inflammation, positive AD biomarkers in body fluids, and developing AD-like pathology in the brain, including A\u03b2 and tau pathology, glial cell activation, and partial synaptic damage, but no neuronal degeneration or death as compared to the healthy normal group. Hereby, we consider the T2DM monkeys with elevation of the peripheral pro-inflammatory factors and positive AD biomarkers can be potentially regarded as a preclinical AD model.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13195-024-01416-9","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T11:01:46Z","timestamp":1709895706000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Characterization of preclinical Alzheimer\u2019s disease model: spontaneous type 2 diabetic cynomolgus monkeys with systemic pro-inflammation, positive biomarkers and developing AD-like pathology"],"prefix":"10.1186","volume":"16","author":[{"given":"Xinxin","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyan","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzhen","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"1416_CR1","unstructured":"Alzheimer\u2019s Disease International. 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