{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:08:07Z","timestamp":1789560487422,"version":"build-2803163510"},"reference-count":74,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007512","name":"Nancy and Buster Alvord Endowment","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007512","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>We investigated whether the cerebellum develops neuropathology that correlates with well\u2010accepted Alzheimer's disease (AD) neuropathological markers and cognitive status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We studied cerebellar cytoarchitecture in a cohort (\n                      <jats:italic>N\u00a0<\/jats:italic>\n                      =\u00a030) of brain donors. In a larger cohort (\n                      <jats:italic>N\u00a0<\/jats:italic>\n                      =\u00a0605), we queried whether the weight of the contents of the posterior fossa (PF), which contains primarily cerebellum, correlated with dementia status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Although there was no granular layer (GL) cell loss, GL area was lower in AD cases, particularly in the lateral cerebellum. Lower numbers of mossy fiber synaptic terminals in the cerebellar GL of AD cases correlated with Braak stages IV\u2013VI. PF content weight correlated with dementia independently of age, neuropathology, and education. In addition, we found that a measure of the relative size of the PF content weight to total brain weight correlated with less dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These results confirm that the cerebellum is not spared neuropathological damage in AD.<\/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>\n                            Novel evidence of cerebellar atrophy in the granule cell layer of the lateral cerebellar cortex (or \u2018cognitive cerebellum\u2019), and loss of a specific cerebellar synapse type in this region, the cerebellar glomerulus. Both correlated with dementia status and Braak stages IV through VI,\n                            <jats:italic>in a cohort with complete neuropathological characterization<\/jats:italic>\n                            . Although there have been recent brain imaging studies suggesting a role for cerebellum in Alzheimer's disease, we believe our study constitutes some of the most concrete neuropathological evidence to date of anatomic and synaptic substrates that are disrupted in AD. These changes in this cerebellar region may even play a role in the etiology of cognitive symptoms.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Novel evidence that individuals with lower postmortem cerebellar weights showed more cognitive decline,\n                            <jats:italic>independent of classical neuropathology markers<\/jats:italic>\n                            such as Braak stage, Thal phase, or Corsortium to Establish a Registry for Alzheimer's Disease (CERAD) score, suggesting a role for this brain region in dementia, using advanced statistical analysis of a large unbiased population cohort (\n                            <jats:italic>n\u00a0<\/jats:italic>\n                            =\u00a0605), the Adult Changes in Thought (ACT) study.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Conversely, a measure of how intact the cerebellum was correlated with\n                            <jats:italic>less<\/jats:italic>\n                            dementia,\n                            <jats:italic>independent of classical neuropathology markers and cerebral cortical weight<\/jats:italic>\n                            , again, in the ACT cohort of 605 brain donors. We believe that this novel finding has relevance and implications for the identification of resilience factors, which may protect against the development of dementia.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14428","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T06:14:57Z","timestamp":1734934497000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Neuropathological correlates of vulnerability and resilience in the cerebellum in Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Colby L.","family":"Samstag","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences University of Washington  Seattle Washington USA"},{"name":"Geriatric Research, Education and 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