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@ARTICLE{Neubauer:281839,
      author       = {Neubauer, Antonia and Weissenbrunner, Doris and Pekrun,
                      Susanna and Roeber, Sigrun and Ruf, Viktoria and Feyen, Paul
                      and Strübing, Felix L and Herms, Jochen},
      title        = {{A}lpha-synuclein deposition patterns in {A}lzheimer's
                      disease: association with cortical amyloid beta and variable
                      tau load.},
      journal      = {Acta neuropathologica},
      volume       = {150},
      number       = {1},
      issn         = {0001-6322},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DZNE-2025-01219},
      pages        = {46},
      year         = {2025},
      abstract     = {Alpha-synuclein (α-syn) deposits are common in around half
                      of the Alzheimer's disease (AD) cases. While direct and
                      indirect protein interactions are suggested, the
                      relationships between different protein aggregates remain
                      poorly understood. Here, we aimed to characterize α-syn,
                      amyloid beta (Aβ), and tau load distributions of AD
                      patients. Protein deposits were automatically quantified
                      with random forest pixel classifiers in immunohistochemical
                      stains of up to 28 brain regions in 72 brains with advanced
                      AD neuropathological change. α-syn-negative cases were
                      distinguished from amygdala predominant, brainstem
                      predominant, and cortical α-syn-positive cases.
                      Relationships with age, sex, and ApoE genotype were
                      examined. α-syn co-pathology was detected in $60\%$ of AD
                      cases, more frequently, although not significantly, in
                      women. Half of these positive cases presented α-syn
                      deposits in the cortex, around one-third predominantly in
                      the amygdala, and the remaining cases primarily in the
                      brainstem. A high α-syn load in the amygdala was associated
                      with an increased cortical Aβ load. The cortical tau load
                      was increased in the amygdala-predominant α-syn group, but
                      decreased in the brainstem-predominant and cortical α-syn
                      cases in comparison with α-syn-negative cases. ApoE4 was
                      associated with higher hippocampal α-syn and cortical Aβ
                      deposition. Younger age at death was associated with a
                      focally higher Aβ and tau load. AD cases with cortical
                      α-syn deposition tended to have a younger age at death.
                      Here, we show that next to age, sex, and ApoE genotype, the
                      α-syn distribution in AD is related to different Aβ and
                      tau loads. This may have therapeutic relevance for
                      identifying patients who respond to Aβ immunotherapy
                      related to tau burden and underpin the need to define α-syn
                      pathology and distribution in early disease stages.},
      keywords     = {Humans / Alzheimer Disease: pathology / Alzheimer Disease:
                      metabolism / Alzheimer Disease: genetics / Female / Male /
                      alpha-Synuclein: metabolism / tau Proteins: metabolism /
                      Amyloid beta-Peptides: metabolism / Aged / Aged, 80 and over
                      / Cerebral Cortex: metabolism / Cerebral Cortex: pathology /
                      Middle Aged / Brain: pathology / Brain: metabolism /
                      Apolipoproteins E: genetics / Alpha-synuclein (Other) /
                      Alzheimer’s disease (Other) / Immunohistochemistry (Other)
                      / Lewy body disease (Other) / Mixed pathology (Other) /
                      Quantitative neuropathology (Other) / alpha-Synuclein (NLM
                      Chemicals) / tau Proteins (NLM Chemicals) / Amyloid
                      beta-Peptides (NLM Chemicals) / Apolipoproteins E (NLM
                      Chemicals) / MAPT protein, human (NLM Chemicals)},
      cin          = {AG Herms},
      ddc          = {610},
      cid          = {I:(DE-2719)1110001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41165827},
      doi          = {10.1007/s00401-025-02952-w},
      url          = {https://pub.dzne.de/record/281839},
}