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Previous proteomic studies using microdissected plaques might have captured non\u2010specific components rather than true A\u03b2 interactors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Biotinylated A\u03b240 or A\u03b242 peptides were induced to form fibrils, with Scrambled peptides as controls, and incubated with protein extracts from AD and control prefrontal cortex tissue. Pull\u2010down assays coupled with label\u2010free proteomics identified fibril interactors. Dysregulation and localization were assessed by Western blot, immunofluorescence, immunocytochemistry, immunohistochemistry, and in silico analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      We identified 185 A\u03b240\u2010 and 874 A\u03b242\u2010associated proteins, with 78 shared. Sixteen proteins, including protein kinase C gamma type (PRKCG), displaying altered expression in AD, were validated as actual interactors and plaque components\n                      <jats:italic>ex vivo<\/jats:italic>\n                      . Remarkably, modulation of PRKCG influenced fibril formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This study expands the A\u03b2 plaque\u2010associated proteome, identifies novel interactors, and highlights PRKCG as a drug\u2010targetable regulator of AD amyloidogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>A comprehensive proteomic profiling allowed identifying proteins interacting with A\u03b240 and A\u03b242 fibrils, including many novel interactors.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Sixteen proteins were validated in vitro and\n                            <jats:italic>ex vivo<\/jats:italic>\n                            as bona fide A\u03b2 plaque constituents.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Dysregulated expression of key interactors was confirmed in AD brain and cell models.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Modulation of PRKCG activity altered A\u03b2 fibril formation and progression.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Findings expand the A\u03b2\u2010associated proteome and highlight novel targets for AD biomarker and therapeutic development.<\/jats:p>\n                        <\/jats:list-item>\n                      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