{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T08:06:44Z","timestamp":1778659604877,"version":"3.51.4"},"reference-count":201,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Lazio, POR FESR Lazio 2014\u20132020","award":["T0002E0001 G04014_13_04_2021"],"award-info":[{"award-number":["T0002E0001 G04014_13_04_2021"]}]},{"name":"Regione Lazio, POR FESR Lazio 2014\u20132020","award":["971925"],"award-info":[{"award-number":["971925"]}]},{"name":"Alzheimer\u2019s Association Research","award":["T0002E0001 G04014_13_04_2021"],"award-info":[{"award-number":["T0002E0001 G04014_13_04_2021"]}]},{"name":"Alzheimer\u2019s Association Research","award":["971925"],"award-info":[{"award-number":["971925"]}]},{"name":"PNRR (National Plan for Recovery and Resilience Next Generation EU)","award":["T0002E0001 G04014_13_04_2021"],"award-info":[{"award-number":["T0002E0001 G04014_13_04_2021"]}]},{"name":"PNRR (National Plan for Recovery and Resilience Next Generation EU)","award":["971925"],"award-info":[{"award-number":["971925"]}]},{"name":"Post-doctoral Fellowship by Operatori Sanitari Associati (OSA)","award":["T0002E0001 G04014_13_04_2021"],"award-info":[{"award-number":["T0002E0001 G04014_13_04_2021"]}]},{"name":"Post-doctoral Fellowship by Operatori Sanitari Associati (OSA)","award":["971925"],"award-info":[{"award-number":["971925"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Beyond deficits in hippocampal-dependent episodic memory, Alzheimer\u2019s Disease (AD) features sensory impairment in visual cognition consistent with extensive neuropathology in the retina. 12A12 is a monoclonal cleavage specific antibody (mAb) that in vivo selectively neutralizes the AD-relevant, harmful N-terminal 20\u201322 kDa tau fragment(s) (i.e., NH2htau) without affecting the full-length normal protein. When systemically injected into the Tg2576 mouse model overexpressing a mutant form of Amyloid Precursor Protein (APP), APPK670\/671L linked to early onset familial AD, this conformation-specific tau mAb successfully reduces the NH2htau accumulating both in their brain and retina and, thus, markedly alleviates the phenotype-associated signs. By means of a combined biochemical and metabolic experimental approach, we report that 12A12mAb downregulates the steady state expression levels of APP and Beta-Secretase 1 (BACE-1) and, thus, limits the Amyloid beta (A\u03b2) production both in the hippocampus and retina from this AD animal model. The local, antibody-mediated anti-amyloidogenic action is paralleled in vivo by coordinated modulation of the endocytic (BIN1, RIN3) and bioenergetic (glycolysis and L-Lactate) pathways. These findings indicate for the first time that similar molecular and metabolic retino-cerebral pathways are modulated in a coordinated fashion in response to 12A12mAb treatment to tackle the neurosensorial A\u03b2 accumulation in AD neurodegeneration.<\/jats:p>","DOI":"10.3390\/ijms24119683","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T10:08:41Z","timestamp":1685700521000},"page":"9683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Cleavage-Specific Tau 12A12mAb Exerts an Anti-Amyloidogenic Action by Modulating the Endocytic and Bioenergetic Pathways in Alzheimer\u2019s Disease Mouse Model"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6057-6154","authenticated-orcid":false,"given":"Valentina","family":"Latina","sequence":"first","affiliation":[{"name":"European Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-6414","authenticated-orcid":false,"given":"Anna","family":"Atlante","sequence":"additional","affiliation":[{"name":"Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), Via Amendola 122\/O, 70126 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8635-8622","authenticated-orcid":false,"given":"Francesca","family":"Malerba","sequence":"additional","affiliation":[{"name":"European Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"La Regina","sequence":"additional","affiliation":[{"name":"European Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2254-1647","authenticated-orcid":false,"given":"Bijorn Omar","family":"Balzamino","sequence":"additional","affiliation":[{"name":"Research Laboratories in Ophthalmology, IRCCS\u2014Fondazione Bietti, Via Santo Stefano Rotondo 6, 00184 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9375-6071","authenticated-orcid":false,"given":"Alessandra","family":"Micera","sequence":"additional","affiliation":[{"name":"Research Laboratories in Ophthalmology, IRCCS\u2014Fondazione Bietti, Via Santo Stefano Rotondo 6, 00184 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annabella","family":"Pignataro","sequence":"additional","affiliation":[{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Fosso del Cavaliere 100, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Egidio","family":"Stigliano","sequence":"additional","affiliation":[{"name":"Area of Pathology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Istituto di Anatomia Patologica, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7590-1792","authenticated-orcid":false,"given":"Sebastiano","family":"Cavallaro","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), Via P. Gaifami 18, 95126 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Calissano","sequence":"additional","affiliation":[{"name":"European Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2080-2951","authenticated-orcid":false,"given":"Giuseppina","family":"Amadoro","sequence":"additional","affiliation":[{"name":"European Brain Research Institute (EBRI), Viale Regina Elena 295, 00161 Rome, Italy"},{"name":"Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Fosso del Cavaliere 100, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nrneurol.2012.227","article-title":"The retina as a window to the brain: From eye research to CNS disorders","volume":"9","author":"London","year":"2013","journal-title":"Nat. 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