{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:05:30Z","timestamp":1747184730627,"version":"3.40.5"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Cerebral amyloid angiopathy (CAA) has been associated with a variety of neurodegenerative disorders, included prion diseases and Alzheimer's disease; its pathophysiology is still largely unknown. We report the case of an 80\u2010year\u2010old man with rapidly progressive dementia and neuroimaging features consistent with CAA carrying two genetic defects in the <jats:italic>PRNP<\/jats:italic> and <jats:italic>SORL1<\/jats:italic> genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Neurological examination, brain magnetic resonance imaging (MRI), electroencephalographic\u2013electromyographic (EEG\u2013EMG) polygraphy, and analysis of 14\u20103\u20103 and tau proteins, A\u03b240, and A\u03b242 in the cerebrospinal fluid (CSF) were performed. The patient underwent a detailed genetic study by next generation sequencing analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient presented with progressive cognitive dysfunction, generalized myoclonus, and ataxia. Approximately 9\u00a0months after symptom onset, he was bed\u2010bound, almost mute, and akinetic. Brain MRI was consistent with CAA. CSF analysis showed high levels of t\u2010tau and p\u2010tau, decreased A\u03b242, decreased A\u03b242\/A\u03b240 ratio, and absence of 14.3.3 protein. EEG\u2013EMG polygraphy demonstrated diffuse slowing, frontal theta activity, and generalized spike\u2010waves related to upper limb myoclonus induced by intermittent photic stimulation. Genetic tests revealed the presence of the E270K variant in the <jats:italic>SORL1<\/jats:italic> gene and the presence of a single octapeptide repeat insertion in the coding region of the <jats:italic>PRNP<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The specific pathogenic contribution of the two DNA variations is difficult to determine without neuropathology; among the possible explanations, we discuss the possibility of their link with CAA. Vascular and degenerative pathways actually interact in a synergistic way, and genetic studies may lead to more insight into pathophysiological mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15487","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T14:08:42Z","timestamp":1657030122000},"page":"3139-3146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp><i>SORL1<\/i><\/scp> gene mutation and octapeptide repeat insertion in <scp><i>PRNP<\/i><\/scp> gene in a case presenting with rapidly progressive dementia and cerebral amyloid angiopathy"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0394-1976","authenticated-orcid":false,"given":"Federica","family":"Cencini","sequence":"first","affiliation":[{"name":"I Clinical Neurology Unit, Department of Health Sciences, Aldo Ravelli Research Centre University of Milan, San Paolo University 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