{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:26:13Z","timestamp":1785277573703,"version":"3.55.0"},"reference-count":108,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most prevalent cause of dementia and can be conceptualized as a tauopathy initiated by the accumulation of amyloid-\u03b2 (A\u03b2) in the brain. The clinical introduction of anti-A\u03b2 antibody therapies has marked the beginning of a new era in disease-modifying treatment for dementia. While the deleterious effects of A\u03b2 on postsynaptic spines and axonal microtubules have been increasingly clarified, recent studies have shifted attention beyond extracellular A\u03b2 deposition as senile plaques to the pathogenic significance of intracellular A\u03b2. In particular, accumulating evidence highlights lysosomes as critical sites of intracellular A\u03b2 toxicity. Interactions between A\u03b2 and gangliosides, v-ATPase-dependent lysosomal acidification, and lysosomal membrane integrity are the key determinants of disease progression. In parallel, additional molecular players, including components of the complement cascade and asparaginyl endopeptidase, have been implicated in linking A\u03b2 pathology to tau dysregulation and neurodegeneration. As therapeutic strategies targeting A\u03b2 enter clinical practice, these emerging pathways represent promising targets for the next generation of AD treatment. Here, we summarize current insights and ongoing therapeutic developments centered on these mechanisms.<\/jats:p>","DOI":"10.3390\/jcm15062357","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:38:01Z","timestamp":1773934681000},"page":"2357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Alzheimer\u2019s Disease: From Pathogenesis to Emerging Therapeutic Targets"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-0842","authenticated-orcid":false,"given":"Tetsuya","family":"Takahashi","sequence":"first","affiliation":[{"name":"MNES Inc., 1-2-27 Shinonome Honmachi, Minami-ku, Hiroshima-shi 734-0023, Hiroshima, Japan"},{"name":"Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashihiroshima-shi 739-2695, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1660-6202","authenticated-orcid":false,"given":"Kazuki","family":"Muguruma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hiroshima City Rehabilitation Hospital, 1-39-1, Tomominami, Asaminami-ku, Hiroshima-shi 731-3168, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lannfelt, L. 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