@article{e494e246d42a4cc78e0a061a989b51e0,
title = "Asymmetry of Hippocampal Tau Pathology in Primary Age-Related Tauopathy and Alzheimer Disease",
abstract = "Primary age-related tauopathy (PART) is a neurodegenerative entity defined as neurofibrillary degeneration generally restricted to the medial temporal region (Braak stage I-IV) with complete or near absence of diffuse and neuritic plaques. Symptoms range in severity but are generally milder and later in onset than in Alzheimer disease (AD). Recently, an early predilection for neurofibrillary degeneration in the hippocampal CA2 subregion has been demonstrated in PART, whereas AD neuropathologic change (ADNC) typically displays relative sparing of CA2 until later stages. In this study, we utilized a semiquantitative scoring system to evaluate asymmetry of neurofibrillary degeneration between left and right hippocampi in 67 PART cases and 17 ADNC cases. 49% of PART cases demonstrated asymmetric findings in at least one hippocampal subregion, and 79% of the asymmetric cases displayed some degree of CA2 asymmetry. Additionally, 19% of cases revealed a difference in Braak score between the right and left hippocampi. There was a significant difference in CA2 neurofibrillary degeneration (p¼0.0006) and CA2/ CA1 ratio (p<0.0001) when comparing the contralateral sides, but neither right nor left was more consistently affected. These data show the importance of analyzing bilateral hippocampi in the diagnostic evaluation of PART and potentially of other neurodegenerative diseases. VC 2021 American Association of Neuropathologists, Inc. All rights reserved.",
keywords = "Alzheimer disease, Braak, CA1, CA2, Neurofibrillary tangles, Primary age-related tauopathy, Thal",
author = "Walker, {Jamie M.} and Yelena Fudym and Kurt Farrell and Iida, {Megan A.} and Bieniek, {Kevin F.} and Sudha Seshadri and White, {Charles L.} and Crary, {John F.} and Richardson, {Timothy E.}",
note = "Funding Information: The authors would like to acknowledge support from The Barker Brain Bank, Reed Precision Medicine Funds, and The Glenn Biggs Institute for Alzheimer{\textquoteright}s and Neurodegenerative Diseases at the Joe and Teresa Long School of Medicine, University of Texas Health San Antonio. In addition, the authors would like to thank all of the brain donors for allowing this work to be possible. Funding Information: Current standard workup for neurodegenerative diseases at most institutions includes only unilateral histologic examination of the hippocampus and neocortex with retention of the opposite hemibrain for nonmorphologic research analyses; this study demonstrates that unilateral examination of some brain regions may mislead the examiner in judging the severity of disease and has potential implications for the staging of PART and ADNC. For more accurate neurolopathogical diagnoses, and a more complete assessment of incidence and severity, a recommendation for bilateral tissue examination is supported by this study. In addition, these findings, along with the more general finding that PART displays an early selective vulnerability of the CA2 hippocampal subfield for neurofibrillary degeneration (, , ), and molecular studies indicating divergent underlying genetic risk factors (, , , , , ), support the hypothesis that PART is a neuropathologically distinct entity from AD. ACKNOWLEDGMENTS Publisher Copyright: {\textcopyright} 2021 Oxford University Press. All rights reserved.",
year = "2021",
month = may,
day = "1",
doi = "10.1093/jnen/nlab032",
language = "English",
volume = "80",
pages = "436--445",
journal = "Journal of Neuropathology and Experimental Neurology",
issn = "0022-3069",
publisher = "Oxford University Press",
number = "5",
}