{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:26:45Z","timestamp":1773055605650,"version":"3.50.1"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:00:00Z","timestamp":1743724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:00:00Z","timestamp":1743724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01AG067426"],"award-info":[{"award-number":["R01AG067426"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01AG067426"],"award-info":[{"award-number":["R01AG067426"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01AG067426"],"award-info":[{"award-number":["R01AG067426"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01AG067426"],"award-info":[{"award-number":["R01AG067426"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01AG067426"],"award-info":[{"award-number":["R01AG067426"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01AG067426"],"award-info":[{"award-number":["R01AG067426"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-95183-8","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T03:32:00Z","timestamp":1743823920000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exome sequencing of a Portuguese cohort of early-onset Alzheimer\u2019s disease implicates the X-linked lysosomal gene GLA"],"prefix":"10.1038","volume":"15","author":[{"given":"Miguel","family":"T\u00e1buas-Pereira","sequence":"first","affiliation":[]},{"given":"Jos\u00e9","family":"Br\u00e1s","sequence":"additional","affiliation":[]},{"given":"Ricardo","family":"Taipa","sequence":"additional","affiliation":[]},{"given":"Kelly","family":"Del Tredici","sequence":"additional","affiliation":[]},{"given":"Kimberly","family":"Paquette","sequence":"additional","affiliation":[]},{"given":"Sophia","family":"Chaudhry","sequence":"additional","affiliation":[]},{"given":"Kaitlyn","family":"DenHaan","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Dur\u00e3es","sequence":"additional","affiliation":[]},{"given":"Marisa","family":"Lima","sequence":"additional","affiliation":[]},{"given":"Catarina","family":"Bernardes","sequence":"additional","affiliation":[]},{"given":"Susana","family":"Carmona","sequence":"additional","affiliation":[]},{"given":"In\u00eas","family":"Baldeiras","sequence":"additional","affiliation":[]},{"given":"Ros\u00e1rio","family":"Almeida","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Santana","sequence":"additional","affiliation":[]},{"given":"Rita","family":"Guerreiro","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"key":"95183_CR1","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1002\/ana.20318","volume":"57","author":"H Petrovitch","year":"2005","unstructured":"Petrovitch, H. et al. AD lesions and infarcts in demented and non-demented Japanese-American men. Ann. Neurol. 57, 98\u2013103. https:\/\/doi.org\/10.1002\/ana.20318 (2005).","journal-title":"Ann. Neurol."},{"key":"95183_CR2","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/jcbfm.2015.164","volume":"36","author":"L Raz","year":"2016","unstructured":"Raz, L., Knoefel, J. & Bhaskar, K. The neuropathology and cerebrovascular mechanisms of dementia. J. Cereb. Blood Flow. Metab. 36, 172\u2013186. https:\/\/doi.org\/10.1038\/jcbfm.2015.164 (2016).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"95183_CR3","doi-asserted-by":"publisher","first-page":"81","DOI":"10.5114\/fn.2018.76610","volume":"56","author":"J De Reuck","year":"2018","unstructured":"De Reuck, J. et al. Aging and cerebrovascular lesions in pure and in mixed neurodegenerative and vascular dementia brains: a neuropathological study. Folia Neuropathol. 56, 81\u201387. https:\/\/doi.org\/10.5114\/fn.2018.76610 (2018).","journal-title":"Folia Neuropathol."},{"key":"95183_CR4","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.3233\/JAD-200473","volume":"76","author":"E Solis","year":"2020","unstructured":"Solis, E., Hascup, K. N. & Hascup, E. R. Alzheimer\u2019s disease: the link between Amyloid-\u03b2 and neurovascular dysfunction. J. Alzheimers Dis. 76, 1179\u20131198. https:\/\/doi.org\/10.3233\/JAD-200473 (2020).","journal-title":"J. Alzheimers Dis."},{"key":"95183_CR5","doi-asserted-by":"publisher","first-page":"795","DOI":"10.3233\/JAD181028","volume":"67","author":"A Serrano-Pozo","year":"2019","unstructured":"Serrano-Pozo, A. & Growdon, J. H. Is Alzheimer\u2019s disease risk modifiable?? J. Alzheimers Dis. 67, 795\u2013819. https:\/\/doi.org\/10.3233\/JAD181028 (2019).","journal-title":"J. Alzheimers Dis."},{"key":"95183_CR6","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.3390\/ijms18091965","volume":"18","author":"Y Yamazaki","year":"2017","unstructured":"Yamazaki, Y. & Kanekiyo, T. Blood-Brain barrier dysfunction and the pathogenesis of Alzheimer\u2019s disease. IJMS 18, 1965. https:\/\/doi.org\/10.3390\/ijms18091965 (2017).","journal-title":"IJMS"},{"key":"95183_CR7","doi-asserted-by":"publisher","first-page":"11934","DOI":"10.1038\/ncomms11934","volume":"7","author":"The Alzheimer\u2019s Disease Neuroimaging Initiative","year":"2016","unstructured":"The Alzheimer\u2019s Disease Neuroimaging Initiative et al. Early role of vascular dysregulation on late-onset Alzheimer\u2019s disease based on multifactorial data-driven analysis. Nat. Commun. 7, 11934. https:\/\/doi.org\/10.1038\/ncomms11934 (2016).","journal-title":"Nat. Commun."},{"key":"95183_CR8","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/S1474-4422(16)30029-1","volume":"15","author":"Z Arvanitakis","year":"2016","unstructured":"Arvanitakis, Z., Capuano, A. W., Leurgans, S. E., Bennett, D. A. & Schneider, J. A. Relation of cerebral vessel disease to Alzheimer\u2019s disease dementia and cognitive function in elderly people: a cross-sectional study. Lancet Neurol. 15, 934\u2013943. https:\/\/doi.org\/10.1016\/S1474-4422(16)30029-1 (2016).","journal-title":"Lancet Neurol."},{"key":"95183_CR9","doi-asserted-by":"publisher","first-page":"2697","DOI":"10.1093\/brain\/awt188","volume":"136","author":"JB Toledo","year":"2013","unstructured":"Toledo, J. B. et al. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer\u2019s coordinating centre. Brain 136, 2697\u20132706. https:\/\/doi.org\/10.1093\/brain\/awt188 (2013).","journal-title":"Brain"},{"key":"95183_CR10","doi-asserted-by":"publisher","unstructured":"Sweeney, M. D. et al. Vascular dysfunction \u2013 the disregarded partner of Alzheimer\u2019s disease, Alzheimers Dement 15 158\u2013167. (2019). https:\/\/doi.org\/10.1016\/j.jalz.2018.07.222","DOI":"10.1016\/j.jalz.2018.07.222"},{"key":"95183_CR11","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1001\/jama.2017.3090","volume":"317","author":"RF Gottesman","year":"2017","unstructured":"Gottesman, R. F. et al. Mosley, association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA 317, 1443\u20131450. https:\/\/doi.org\/10.1001\/jama.2017.3090 (2017).","journal-title":"JAMA"},{"key":"95183_CR12","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1002\/ana.25071","volume":"82","author":"P Vemuri","year":"2017","unstructured":"Vemuri, P. et al. Age, vascular health, and alzheimer disease biomarkers in an elderly sample. Ann. Neurol. 82, 706\u2013718. https:\/\/doi.org\/10.1002\/ana.25071 (2017).","journal-title":"Ann. Neurol."},{"key":"95183_CR13","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1002\/ana.24647","volume":"79","author":"S Lee","year":"2016","unstructured":"Lee, S. et al. Dominantly inherited alzheimer network, white matter hyperintensities are a core feature of alzheimer\u2019s disease: evidence from the dominantly inherited alzheimer network. Ann. Neurol. 79, 929\u2013939. https:\/\/doi.org\/10.1002\/ana.24647 (2016).","journal-title":"Ann. Neurol."},{"key":"95183_CR14","doi-asserted-by":"crossref","first-page":"179e17","DOI":"10.1016\/j.neurobiolaging.2018.01.015","volume":"66","author":"C Sassi","year":"2018","unstructured":"Sassi, C. et al. Mendelian adult-onset leukodystrophy genes in Alzheimer\u2019s disease: critical influence of CSF1R and NOTCH3. Neurobiol. Aging. 66, 179e17\u2013179179. .e29 (2018).","journal-title":"Neurobiol. Aging"},{"key":"95183_CR15","doi-asserted-by":"publisher","first-page":"e191350","DOI":"10.1001\/jamanetworkopen.2019.1350","volume":"2","author":"D Patel","year":"2019","unstructured":"Patel, D. et al. Association of rare coding mutations with alzheimer disease and other dementias among adults of European ancestry. JAMA Netw. Open. 2, e191350. https:\/\/doi.org\/10.1001\/jamanetworkopen.2019.1350 (2019).","journal-title":"JAMA Netw. Open."},{"key":"95183_CR16","doi-asserted-by":"publisher","first-page":"460","DOI":"10.4172\/2161-0460.1000460","volume":"9","author":"C Pang","year":"2019","unstructured":"Pang, C. et al. Identification and analysis of Alzheimer\u2019s candidate genes by an amplitude deviation algorithm. J. Alzheimers Dis. Parkinsonism. 9, 460. https:\/\/doi.org\/10.4172\/2161-0460.1000460 (2019).","journal-title":"J. Alzheimers Dis. Parkinsonism"},{"key":"95183_CR17","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/19083","volume":"398","author":"B De Strooper","year":"1999","unstructured":"De Strooper, B. et al. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518\u2013522. https:\/\/doi.org\/10.1038\/19083 (1999).","journal-title":"Nature"},{"key":"95183_CR18","doi-asserted-by":"publisher","first-page":"9473","DOI":"10.1021\/jacs.6b03463","volume":"138","author":"Q Chu","year":"2016","unstructured":"Chu, Q. et al. HtrA1 proteolysis of ApoE in vitro is allele selective. J. Am. Chem. Soc. 138, 9473\u20139478. https:\/\/doi.org\/10.1021\/jacs.6b03463 (2016).","journal-title":"J. Am. Chem. Soc."},{"key":"95183_CR19","doi-asserted-by":"publisher","first-page":"1025740","DOI":"10.3389\/fphar.2022.1025740","volume":"13","author":"X Li","year":"2022","unstructured":"Li, X. et al. Fabry disease: mechanism and therapeutics strategies. Front. Pharmacol. 13, 1025740. https:\/\/doi.org\/10.3389\/fphar.2022.1025740 (2022).","journal-title":"Front. Pharmacol."},{"key":"95183_CR20","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","volume":"7","author":"GM McKhann","year":"2011","unstructured":"McKhann, G. M. et al. The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimers Dement. 7, 263\u2013269. https:\/\/doi.org\/10.1016\/j.jalz.2011.03.005 (2011).","journal-title":"Alzheimers Dement."},{"key":"95183_CR21","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1161\/01.STR.0000083050.44441.10","volume":"34","author":"ECW van Straaten","year":"2003","unstructured":"van Straaten, E. C. W. et al. Operational definitions for the NINDS-AIREN criteria for vascular dementia. Stroke 34, 1907\u20131912. https:\/\/doi.org\/10.1161\/01.STR.0000083050.44441.10 (2003).","journal-title":"Stroke"},{"key":"95183_CR22","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna, A. et al. The genome analysis toolkit: A mapreduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297\u20131303. https:\/\/doi.org\/10.1101\/gr.107524.110 (2010).","journal-title":"Genome Res."},{"key":"95183_CR23","doi-asserted-by":"publisher","unstructured":"Auwera, G. A. et al. From FastQ data to High\u2010Confidence variant calls: the genome analysis toolkit best practices pipeline. Curr. Protocols Bioinf. 43 https:\/\/doi.org\/10.1002\/0471250953.bi1110s43 (2013).","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"95183_CR24","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4161\/fly.19695","volume":"6","author":"P Cingolani","year":"2012","unstructured":"Cingolani, P. et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of drosophila melanogaster strain W 1118; iso-2; iso-3. Fly 6, 80\u201392. https:\/\/doi.org\/10.4161\/fly.19695 (2012).","journal-title":"Fly"},{"key":"95183_CR25","doi-asserted-by":"publisher","first-page":"E2393","DOI":"10.1002\/humu.22376","volume":"34","author":"X Liu","year":"2013","unstructured":"Liu, X., Jian, X. & Boerwinkle, E. DbNSFP v2.0: A database of human Non-synonymous SNVs and their functional predictions and annotations. Hum. Mutat. 34, E2393\u2013E2402. https:\/\/doi.org\/10.1002\/humu.22376 (2013).","journal-title":"Hum. Mutat."},{"key":"95183_CR26","doi-asserted-by":"publisher","unstructured":"Patel, Z. H. et al. hbGerard The struggle to find reliable results in exome sequencing data: filtering out Mendelian errors, Front. Genet. 5 (2014). https:\/\/doi.org\/10.3389\/fgene.2014.00016","DOI":"10.3389\/fgene.2014.00016"},{"key":"95183_CR27","doi-asserted-by":"publisher","first-page":"2867","DOI":"10.1093\/bioinformatics\/btq559","volume":"26","author":"A Manichaikul","year":"2010","unstructured":"Manichaikul, A. et al. Robust relationship inference in genome-wide association studies. Bioinformatics 26, 2867\u20132873. https:\/\/doi.org\/10.1093\/bioinformatics\/btq559 (2010).","journal-title":"Bioinformatics"},{"key":"95183_CR28","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1111\/ene.14183","volume":"27","author":"M Mancuso","year":"2020","unstructured":"Mancuso, M. et al. Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European academy of neurology. Eur. J. Neurol. 27, 909\u2013927. https:\/\/doi.org\/10.1111\/ene.14183 (2020).","journal-title":"Eur. J. Neurol."},{"key":"95183_CR29","doi-asserted-by":"publisher","first-page":"104946","DOI":"10.1016\/j.nbd.2020.104946","volume":"142","author":"R Guerreiro","year":"2020","unstructured":"Guerreiro, R. et al. Genetic architecture of common non-Alzheimer\u2019s disease dementias. Neurobiol. Dis. 142, 104946. https:\/\/doi.org\/10.1016\/j.nbd.2020.104946 (2020).","journal-title":"Neurobiol. Dis."},{"key":"95183_CR30","doi-asserted-by":"publisher","unstructured":"T\u00e1buas-Pereira, M. et al. Exome sequencing of a Portuguese cohort of frontotemporal dementia patients: looking into the ALS-FTD continuum. Front. Neurol. 13 https:\/\/doi.org\/10.3389\/fneur.2022.886379 (2022).","DOI":"10.3389\/fneur.2022.886379"},{"key":"95183_CR31","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1101\/gr.176601","volume":"11","author":"PC Ng","year":"2001","unstructured":"Ng, P. C. & Henikoff, S. Predicting deleterious amino acid substitutions. Genome Res. 11, 863\u2013874. https:\/\/doi.org\/10.1101\/gr.176601 (2001).","journal-title":"Genome Res."},{"key":"95183_CR32","doi-asserted-by":"crossref","unstructured":"I. Adzhubei, D.M. Jordan, S.R. Sunyaev, Predicting Functional Effect of Human Missense Mutations Using PolyPhen-2, Current Protocols in Human Genetics \/ Editorial Board,Jonathan L. Haines \u2026 et Al.] 0 7 (2013) Unit7.20. https:\/\/doi.org\/10.1002\/0471142905.hg0720s76.","DOI":"10.1002\/0471142905.hg0720s76"},{"key":"95183_CR33","doi-asserted-by":"publisher","first-page":"e46688","DOI":"10.1371\/journal.pone.0046688","volume":"7","author":"Y Choi","year":"2012","unstructured":"Choi, Y., Sims, G. E., Murphy, S., Miller, J. R. & Chan, A. P. Predicting the functional effect of amino acid substitutions and indels. PLoS One. 7, e46688. https:\/\/doi.org\/10.1371\/journal.pone.0046688 (2012).","journal-title":"PLoS One"},{"key":"95183_CR34","doi-asserted-by":"publisher","unstructured":"Steinhaus, R. et al. MutationTaster Nucleic Acids Research 49 (2021) W446\u2013W451. (2021). https:\/\/doi.org\/10.1093\/nar\/gkab266","DOI":"10.1093\/nar\/gkab266"},{"key":"95183_CR35","doi-asserted-by":"publisher","first-page":"D1143","DOI":"10.1093\/nar\/gkad989","volume":"52","author":"M Schubach","year":"2024","unstructured":"Schubach, M., Maass, T., Nazaretyan, L., R\u00f6ner, S. & Kircher, M. CADD v1.7: using protein Language models, regulatory CNNs and other nucleotide-level scores to improve genome-wide variant predictions. Nucleic Acids Res. 52, D1143\u2013D1154. https:\/\/doi.org\/10.1093\/nar\/gkad989 (2024).","journal-title":"Nucleic Acids Res."},{"key":"95183_CR36","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s00401-006-0127-z","volume":"112","author":"H Braak","year":"2006","unstructured":"Braak, H. et al. Staging of alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 112, 389\u2013404. https:\/\/doi.org\/10.1007\/s00401-006-0127-z (2006).","journal-title":"Acta Neuropathol."},{"key":"95183_CR37","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1212\/wnl.58.12.1791","volume":"58","author":"DR Thal","year":"2002","unstructured":"Thal, D. R., R\u00fcb, U., Orantes, M. & Braak, H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58, 1791\u20131800. https:\/\/doi.org\/10.1212\/wnl.58.12.1791 (2002).","journal-title":"Neurology"},{"key":"95183_CR38","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1002\/ana.410300503","volume":"30","author":"JP Vonsattel","year":"1991","unstructured":"Vonsattel, J. P. et al. Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann. Neurol. 30, 637\u2013649. https:\/\/doi.org\/10.1002\/ana.410300503 (1991).","journal-title":"Ann. Neurol."},{"key":"95183_CR39","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/s0197-4580(02)00065-9","volume":"24","author":"H Braak","year":"2003","unstructured":"Braak, H. et al. Staging of brain pathology related to sporadic Parkinson\u2019s disease. Neurobiol. Aging. 24, 197\u2013211. https:\/\/doi.org\/10.1016\/s0197-4580(02)00065-9 (2003).","journal-title":"Neurobiol. Aging"},{"key":"95183_CR40","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1681\/ASN.2016090964","volume":"28","author":"M Arends","year":"2017","unstructured":"Arends, M. et al. Characterization of classical and nonclassical Fabry disease: A multicenter study. J. Am. Soc. Nephrol. 28, 1631\u20131641. https:\/\/doi.org\/10.1681\/ASN.2016090964 (2017).","journal-title":"J. Am. Soc. Nephrol."},{"key":"95183_CR41","doi-asserted-by":"publisher","first-page":"1014950","DOI":"10.1155\/2022\/1014950","volume":"2022","author":"A Lackova","year":"2022","unstructured":"Lackova, A. et al. Prevalence of Fabry disease among patients with Parkinson\u2019s disease. Parkinsons Dis. 2022, 1014950. https:\/\/doi.org\/10.1155\/2022\/1014950 (2022).","journal-title":"Parkinsons Dis."},{"key":"95183_CR42","doi-asserted-by":"publisher","unstructured":"Gago, M. F. et al. Parkinson\u2019s disease and Fabry disease: clinical, biochemical and neuroimaging analysis of three pedigrees. J. Parkinsons Dis. 10 (n D) 141\u2013152. https:\/\/doi.org\/10.3233\/JPD-191704","DOI":"10.3233\/JPD-191704"},{"key":"95183_CR43","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1002\/mds.29686","volume":"39","author":"S M\u00fcller","year":"2024","unstructured":"M\u00fcller, S. et al. Del Tredici, Morbus Fabry and Parkinson\u2019s Disease-More evidence for a possible genetic link. Mov. Disord. 39, 449\u2013451. https:\/\/doi.org\/10.1002\/mds.29686 (2024).","journal-title":"Mov. Disord"},{"key":"95183_CR44","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.nbd.2017.11.006","volume":"110","author":"MP Nelson","year":"2018","unstructured":"Nelson, M. P. et al. The lysosomal enzyme alpha-Galactosidase A is deficient in Parkinson\u2019s disease brain in association with the pathologic accumulation of alpha-synuclein. Neurobiol. Dis. 110, 68\u201381. https:\/\/doi.org\/10.1016\/j.nbd.2017.11.006 (2018).","journal-title":"Neurobiol. Dis."},{"key":"95183_CR45","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1111\/j.1440-1789.2008.00883.x","volume":"28","author":"R Okeda","year":"2008","unstructured":"Okeda, R. & Nisihara, M. An autopsy case of Fabry disease with neuropathological investigation of the pathogenesis of associated dementia. Neuropathology 28, 532\u2013540. https:\/\/doi.org\/10.1111\/j.1440-1789.2008.00883.x (2008).","journal-title":"Neuropathology"},{"key":"95183_CR46","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1093\/jnen\/nlz139","volume":"79","author":"K Del Tredici","year":"2020","unstructured":"Del Tredici, K. et al. Fabry disease with concomitant lewy body disease. J. Neuropathol. Exp. Neurol. 79, 378\u2013392. https:\/\/doi.org\/10.1093\/jnen\/nlz139 (2020).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"95183_CR47","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1007\/s13244-018-0664-8","volume":"9","author":"S Cocozza","year":"2018","unstructured":"Cocozza, S., Russo, C., Pontillo, G., Pisani, A. & Brunetti, A. Neuroimaging in Fabry disease: current knowledge and future directions. Insights Imaging. 9, 1077\u20131088. https:\/\/doi.org\/10.1007\/s13244-018-0664-8 (2018).","journal-title":"Insights Imaging"},{"key":"95183_CR48","doi-asserted-by":"publisher","unstructured":"Moreno-Grau, S. et al. GR@ACE study group, DEGESCO consortium,,,,,,, Alzheimer\u2019s Disease Neuroimaging Initiative, Long runs of homozygosity are associated with Alzheimer\u2019s disease, Transl Psychiatry 11 142. (2021). https:\/\/doi.org\/10.1038\/s41398-020-01145-1","DOI":"10.1038\/s41398-020-01145-1"},{"key":"95183_CR49","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12673-x","author":"M T\u00e1buas-Pereira","year":"2024","unstructured":"T\u00e1buas-Pereira, M. et al. Exploring first-degree family history in a cohort of Portuguese Alzheimer\u2019s disease patients: population evidence for X-chromosome linked and recessive inheritance of risk factors. J. Neurol. https:\/\/doi.org\/10.1007\/s00415-024-12673-x (2024).","journal-title":"J. Neurol."},{"key":"95183_CR50","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.ymgme.2014.11.004","volume":"114","author":"S Ferreira","year":"2015","unstructured":"Ferreira, S. et al. The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies. Mol. Genet. Metab. 114, 248\u2013258. https:\/\/doi.org\/10.1016\/j.ymgme.2014.11.004 (2015).","journal-title":"Mol. Genet. Metab."},{"key":"95183_CR51","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1161\/STROKEAHA.109.570499","volume":"41","author":"MV Baptista","year":"2010","unstructured":"Baptista, M. V. et al. PORTuguese young STROKE investigators, mutations of the GLA gene in young patients with stroke: the PORTYSTROKE study\u2013screening genetic conditions in Portuguese young stroke patients. Stroke 41, 431\u2013436. https:\/\/doi.org\/10.1161\/STROKEAHA.109.570499 (2010).","journal-title":"Stroke"},{"key":"95183_CR52","doi-asserted-by":"publisher","first-page":"e981","DOI":"10.1002\/mgg3.981","volume":"7","author":"M Cer\u00f3n-Rodr\u00edguez","year":"2019","unstructured":"Cer\u00f3n-Rodr\u00edguez, M., Ram\u00f3n-Garc\u00eda, G., Barajas-Col\u00f3n, E., Franco-\u00c1lvarez, I. & Salgado-Loza, J. L. Renal globotriaosylceramide deposits for Fabry disease linked to uncertain pathogenicity gene variant c.352C\u2009>\u2009T\/p.Arg118Cys: A family study. Mol. Genet. Genomic Med. 7, e981. https:\/\/doi.org\/10.1002\/mgg3.981 (2019).","journal-title":"Mol. Genet. Genomic Med."},{"key":"95183_CR53","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s13023-018-0792-8","volume":"13","author":"I Vieitez","year":"2018","unstructured":"Vieitez, I. et al. Fabry disease in the Spanish population: observational study with detection of 77 patients. Orphanet J. Rare Dis. 13, 52. https:\/\/doi.org\/10.1186\/s13023-018-0792-8 (2018).","journal-title":"Orphanet J. Rare Dis."},{"key":"95183_CR54","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1056\/NEJMoa0901281","volume":"361","author":"E Sidransky","year":"2009","unstructured":"Sidransky, E. et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson\u2019s disease. N Engl. J. Med. 361, 1651\u20131661. https:\/\/doi.org\/10.1056\/NEJMoa0901281 (2009).","journal-title":"N Engl. J. Med."},{"key":"95183_CR55","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.3390\/cells11081261","volume":"11","author":"L Smith","year":"2022","unstructured":"Smith, L. & Schapira, A. H. V. Variants and Parkinson disease: mechanisms and treatments. Cells 11, 1261. https:\/\/doi.org\/10.3390\/cells11081261 (2022).","journal-title":"Cells"},{"key":"95183_CR56","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1093\/brain\/awn364","volume":"132","author":"S Tikka","year":"2009","unstructured":"Tikka, S. et al. Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients. Brain 132, 933\u2013939. https:\/\/doi.org\/10.1093\/brain\/awn364 (2009).","journal-title":"Brain"},{"key":"95183_CR57","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1385\/JMN:17:2:171","volume":"17","author":"D Hartmann","year":"2001","unstructured":"Hartmann, D., Tournoy, J., Saftig, P., Annaert, W. & De Strooper, B. Implication of APP secretases in Notch signaling. J. Mol. Neurosci. 17, 171\u2013181. https:\/\/doi.org\/10.1385\/JMN:17:2:171 (2001).","journal-title":"J. Mol. Neurosci."},{"key":"95183_CR58","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1016\/j.str.2015.05.001","volume":"23","author":"X Xu","year":"2015","unstructured":"Xu, X. et al. Insights into autoregulation of Notch3 from structural and functional studies of its negative regulatory region. Structure 23, 1227\u20131235. https:\/\/doi.org\/10.1016\/j.str.2015.05.001 (2015).","journal-title":"Structure"},{"key":"95183_CR59","doi-asserted-by":"publisher","unstructured":"C, B. P. L. J. O., K, P. & U, L. The origin of the Ankyrin repeat region in Notch intracellular domains is critical for regulation of HES promoter activity. Mech. Dev. 104 https:\/\/doi.org\/10.1016\/s0925-4773(01)00373-2 (2001).","DOI":"10.1016\/s0925-4773(01)00373-2"},{"key":"95183_CR60","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3389\/fnmol.2014.00046","volume":"7","author":"M Llorens-Mart\u00edn","year":"2014","unstructured":"Llorens-Mart\u00edn, M., Jurado, J., Hern\u00e1ndez, F. & Avila, J. GSK-3\u03b2, a pivotal kinase in alzheimer disease. Front. Mol. Neurosci. 7, 46. https:\/\/doi.org\/10.3389\/fnmol.2014.00046 (2014).","journal-title":"Front. Mol. Neurosci."},{"key":"95183_CR61","doi-asserted-by":"publisher","first-page":"1008e17","DOI":"10.1016\/j.neurobiolaging.2011.10.009","volume":"33","author":"RJ Guerreiro","year":"2012","unstructured":"Guerreiro, R. J. et al. Exome sequencing reveals an unexpected genetic cause of disease: NOTCH3 mutation in a Turkish family with Alzheimer\u2019s disease. Neurobiol. Aging. 33, 1008e17\u20131008e23. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2011.10.009 (2012).","journal-title":"Neurobiol. Aging"},{"key":"95183_CR62","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1158\/1078-0432.CCR-14-1348","volume":"21","author":"K Wang","year":"2015","unstructured":"Wang, K. et al. PEST domain mutations in Notch receptors comprise an oncogenic driver segment in triple-negative breast cancer sensitive to a \u03b3-secretase inhibitor. Clin. Cancer Res. 21, 1487\u20131496. https:\/\/doi.org\/10.1158\/1078-0432.CCR-14-1348 (2015).","journal-title":"Clin. Cancer Res."},{"key":"95183_CR63","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.nbd.2014.12.018","volume":"75","author":"F Ehret","year":"2015","unstructured":"Ehret, F. et al. Mouse model of CADASIL reveals novel insights into Notch3 function in adult hippocampal neurogenesis. Neurobiol. Dis. 75, 131\u2013141. https:\/\/doi.org\/10.1016\/j.nbd.2014.12.018 (2015).","journal-title":"Neurobiol. Dis."},{"key":"95183_CR64","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1111\/cns.13647","volume":"27","author":"L Guo","year":"2021","unstructured":"Guo, L. et al. The role of NOTCH3 variants in Alzheimer\u2019s disease and subcortical vascular dementia in the Chinese population. CNS Neurosci. Ther. 27, 930\u2013940. https:\/\/doi.org\/10.1111\/cns.13647 (2021).","journal-title":"CNS Neurosci. Ther."},{"key":"95183_CR65","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/gim.2014.210","volume":"17","author":"MEC Meuwissen","year":"2015","unstructured":"Meuwissen, M. E. C. et al. The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature. Genet. Med. 17, 843\u2013853. https:\/\/doi.org\/10.1038\/gim.2014.210 (2015).","journal-title":"Genet. Med."},{"key":"95183_CR66","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1093\/brain\/awv155","volume":"138","author":"E Verdura","year":"2015","unstructured":"Verdura, E. et al. Heterozygous HTRA1 mutations are associated with autosomal dominant cerebral small vessel disease. Brain 138, 2347\u20132358. https:\/\/doi.org\/10.1093\/brain\/awv155 (2015).","journal-title":"Brain"},{"key":"95183_CR67","doi-asserted-by":"publisher","first-page":"545","DOI":"10.3389\/fneur.2020.00545","volume":"11","author":"M Uemura","year":"2020","unstructured":"Uemura, M. et al. HTRA1-Related cerebral small vessel disease: A review of the literature. Front. Neurol. 11, 545. https:\/\/doi.org\/10.3389\/fneur.2020.00545 (2020).","journal-title":"Front. Neurol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95183-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95183-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95183-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T03:32:18Z","timestamp":1743823938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-95183-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,4]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["95183"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-95183-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,4]]},"assertion":[{"value":"19 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11653"}}