{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:01:22Z","timestamp":1777395682555,"version":"3.51.4"},"reference-count":72,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,8,17]]},"abstract":"<jats:p>Brain proteins function in their soluble, native conformation and cease to function when transformed into insoluble aggregates, also known as amyloids. Biophysically, the soluble-to-insoluble phase transformation represents a process of polymerization, similar to crystallization, dependent on such extrinsic factors as concentration, pH, and a nucleation surface. The resulting cross-\u03b2 conformation of the insoluble amyloid is markedly stable, making it an unlikely source of toxicity. The spread of brain amyloidosis can be fully explained by mechanisms of spontaneous or catalyzed polymerization and phase transformation instead of active replication, which is an enzyme- and energy-requiring process dependent on a specific nucleic acid code for the transfer of biological information with high fidelity. Early neuronal toxicity in Alzheimer\u2019s disease may therefore be mediated to a greater extent by a reduction in the pool of soluble, normal-functioning protein than its accumulation in the polymerized state. This alternative loss-of-function hypothesis of pathogenicity can be examined by assessing the clinical and neuroimaging effects of administering non-aggregating peptide analogs to replace soluble amyloid-\u03b2 levels above the threshold below which neuronal toxicity may occur. Correcting the depletion of soluble amyloid-\u03b2, however, would only exemplify \u2018rescue medicine.\u2019 Precision medicine will necessitate identifying the pathogenic factors catalyzing the protein aggregation in each affected individual. Only then can we stratify patients for etiology-specific treatments and launch precision medicine for Alzheimer\u2019s disease and other neurodegenerative disorders.<\/jats:p>","DOI":"10.3233\/jad-210415","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T14:04:37Z","timestamp":1623765877000},"page":"1403-1415","source":"Crossref","is-referenced-by-count":46,"title":["Soluble Amyloid-\u03b2 Consumption in Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"82","author":[{"given":"Alberto J.","family":"Espay","sequence":"first","affiliation":[{"name":"James J. and Joan A. 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