{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:16:45Z","timestamp":1791213405827,"version":"4.1.0"},"reference-count":85,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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>Some individuals show intact cognition despite the presence of neuropathological hallmarks of Alzheimer's disease (AD). The plasticity of parvalbumin (PV)\u2010containing interneurons might contribute to resilience. Perineuronal nets (PNNs), that is, extracellular matrix structures around neurons, modulate PV neuron function. We hypothesize that PNNs play a role in resilience to AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>PNN amount and morphology were determined in immunolabelled sections of the frontal cortex of control, AD and resilient subjects. Expression levels of genes related to PNNs and microglia signatures were evaluated by bulk RNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The expression of the PNN\u2010component aggrecan around PV neurons is decreased in resilient and AD subjects, whereas PNN\u2010sugar chains are reduced only in resilient subjects. In AD, fewer presynaptic terminals on PV neurons are detected and genes related to PNN degradation are upregulated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These data show distinct PNN changes in individuals resilient to AD, which may contribute to preserved cognition despite the neuropathology.<\/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>Aggrecan levels are decreased in the frontal cortex of AD and resilient subjects.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In resilient subjects, WFA+ PNNs are reduced around neuronal somata.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In AD patients, PV neurons show disrupted WFA peridendritic staining and synaptic loss.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Expression levels of PNN\u2010degrading enzymes are higher in AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Excitatory neurons bearing a PNN show low amounts of ptau.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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