biostudies-literatureFerrer ILa Caixa FoundationInstituto de Salud Carlos III6427https://www.ebi.ac.uk/biostudies/studies/S-EPMC9223516biostudies-literatureUnknown23(12)Altered protein phosphorylation is a major pathologic modification in tauopathies and Alzheimer's disease (AD) linked to abnormal tau fibrillar deposits in neurofibrillary tangles (NFTs) and pre-tangles and β-amyloid deposits in AD. hTau transgenic mice, which express 3R and less 4R human tau with no mutations in a murine knock-out background, show increased tau deposition in neurons but not NFTs and pre-tangles at the age of nine months. Label-free (phospho)proteomics and SWATH-MS identified 2065 proteins in hTau and wild-type (WT) mice. Only six proteins showed increased levels in hTau; no proteins were down-regulated. Increased tau phosphorylation in hTau was detected at Ser199, Ser202, Ser214, Ser396, Ser400, Thr403, Ser404, Ser413, Ser416, Ser422, Ser491, and Ser494, in addition to ThInternational journal of molecular sciencesDysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model.PMC9223516PT17/0019/009LCF/PR/HR19/52160007Ferrer ICartas-Cejudo PLachen-Montes MDel Rio JAFernandez-Irigoyen JSantamaria EAusin KAndres-Benito PfalseDysregulated Brain Protein Phosphorylation Linked to Increased Human Tau Expression in the hTau Transgenic Mouse Model.Altered protein phosphorylation is a major pathologic modification in tauopathies and Alzheimer's disease (AD) linked to abnormal tau fibrillar deposits in neurofibrillary tangles (NFTs) and pre-tangles and β-amyloid deposits in AD. hTau transgenic mice, which express 3R and less 4R human tau with no mutations in a murine knock-out background, show increased tau deposition in neurons but not NFTs and pre-tangles at the age of nine months. Label-free (phospho)proteomics and SWATH-MS identified 2065 proteins in hTau and wild-type (WT) mice. Only six proteins showed increased levels in hTau; no proteins were down-regulated. Increased tau phosphorylation in hTau was detected at Ser199, Ser202, Ser214, Ser396, Ser400, Thr403, Ser404, Ser413, Ser416, Ser422, Ser491, and Ser494, in addition to Th2022-01-01T00:00:00Z2022 Jun2025-04-04T08:48:11.059Z2025-04-04T08:48:11.059ZS-EPMC92235163574287110.3390/ijms23126427