{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:01:51Z","timestamp":1789084911940,"version":"build-2803163510"},"reference-count":45,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2020,10,27]]},"abstract":"<jats:p>Just as multiple sclerosis (MS) has long been primarily considered a white matter (WM) disease, Alzheimer\u2019s disease (AD) has for decades been regarded only as a grey matter disorder. However, convergent evidences have suggested that WM abnormalities are also important components of AD, at the same extent as axonal and neuronal loss is critically involved in MS pathophysiology since early clinical stages. These observations have motivated a more thorough investigation about the possible mechanisms that could link neuroinflammation and neurodegeneration, focusing on amyloid-\u03b2 (A\u03b2). Neuroimaging studies have found that patients with AD have widespread WM abnormalities already at the earliest disease stages and prior to the presence of A\u03b2 plaques. Moreover, a correlation between cerebrospinal fluid (CSF) A\u03b2 levels and WM lesion load was found. On the other hand, recent studies suggest a predictive role for CSF A\u03b2 levels in MS, possibly due in the first instance to the reduced capacity for remyelination, consequently to a higher risk of WM damage progression, and ultimately to neuronal loss. We undertook a review of the recent findings concerning the involvement of CSF A\u03b2 levels in the MS disease course and of the latest evidence of AD related WM abnormalities, with the aim to discuss the potential causes that may connect WM damage and amyloid pathology.<\/jats:p>","DOI":"10.3233\/jad-200868","type":"journal-article","created":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T11:03:53Z","timestamp":1599563033000},"page":"13-22","source":"Crossref","is-referenced-by-count":28,"title":["The Role of Amyloid-\u03b2 in White Matter Damage: Possible Common Pathogenetic Mechanisms in Neurodegenerative and Demyelinating Diseases"],"prefix":"10.1177","volume":"78","author":[{"given":"Anna M.","family":"Pietroboni","sequence":"first","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, Italy"},{"name":"University of Milan, Dino Ferrari Centre, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Colombi","sequence":"additional","affiliation":[{"name":"University of Milan, Dino Ferrari Centre, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Carandini","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, Italy"},{"name":"University of Milan, Dino Ferrari Centre, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elio","family":"Scarpini","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, Italy"},{"name":"University of Milan, Dino Ferrari Centre, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Milan, Italy"},{"name":"University of Milan, Dino Ferrari Centre, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Bozzali","sequence":"additional","affiliation":[{"name":"Department of Neuroscience \u2018Rita Levi Montalcini\u2019, University of Torino, Turin, Italy"},{"name":"Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-200868_ref1","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1074\/jbc.M113.498246","article-title":"Characterization of intermediate steps in amyloid beta (Abeta) production under near-native conditions","volume":"289","author":"Olsson","year":"2014","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-200868_ref2","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/aps.2017.28","article-title":"Amyloid beta: Structure, biology and structure-based therapeutic development","volume":"38","author":"Chen","year":"2017","journal-title":"Acta Pharmacol Sin"},{"key":"10.3233\/JAD-200868_ref3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/72237","article-title":"Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition","volume":"6","author":"Iwata","year":"2000","journal-title":"Nat Med"},{"key":"10.3233\/JAD-200868_ref4","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/325733a0","article-title":"The precursor of Alzheimer\u2019s disease amyloid A4 protein resembles a cell-surface receptor","volume":"325","author":"Kang","year":"1987","journal-title":"Nature"},{"key":"10.3233\/JAD-200868_ref5","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.str.2010.08.009","article-title":"Biology of amyloid: Structure, function, and regulation","volume":"18","author":"Greenwald","year":"2010","journal-title":"Structure"},{"key":"10.3233\/JAD-200868_ref6","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0165-6147(91)90609-V","article-title":"Amyloid deposition as the central event in the etiology of Alzheimer\u2019s disease","volume":"12","author":"Hardy","year":"1991","journal-title":"Trends Pharmacol Sci"},{"key":"10.3233\/JAD-200868_ref7","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/373523a0","article-title":"Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein","volume":"373","author":"Games","year":"1995","journal-title":"Nature"},{"key":"10.3233\/JAD-200868_ref8","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/jnc.12466","article-title":"Autosomal-dominant Alzheimer\u2019s disease mutations at the same codon of amyloid precursor protein differentially alter A beta production","volume":"128","author":"Su\u00e1rez-Calvet","year":"2014","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-200868_ref9","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2214\/ajr.149.2.351","article-title":"MR signal abnormalities at 1.5 T in Alzheimer\u2019s dementia and normal aging","volume":"149","author":"Fazekas","year":"1987","journal-title":"AJR Am J Roentgenol"},{"key":"10.3233\/JAD-200868_ref10","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1159\/000441422","article-title":"Insights into white matter damage in Alzheimer\u2019s disease: From postmortem to in vivo diffusion tensor MRI studies","volume":"16","author":"Caso","year":"2016","journal-title":"Neurodegener Dis"},{"key":"10.3233\/JAD-200868_ref11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1365-2990.2010.01139.x","article-title":"Review: Cerebral microvascular pathology in ageing and neurodegeneration","volume":"37","author":"Brown","year":"2011","journal-title":"Neuropathol Appl Neurobiol"},{"key":"10.3233\/JAD-200868_ref12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1159\/000063606","article-title":"Cerebral amyloid angiopathy, white matter lesions and Alzheimer encephalopathy \u2013a histopathological assessment","volume":"14","author":"Haglund","year":"2002","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.3233\/JAD-200868_ref13","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1093\/brain\/awy153","article-title":"A broader view of dementia: Multiple co-pathologies are the norm","volume":"141","author":"Coulthard","year":"2018","journal-title":"Brain"},{"key":"10.3233\/JAD-200868_ref14","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.2353\/ajpath.2010.100087","article-title":"Early oligodendrocyte\/myelin pathology in Alzheimer\u2019s disease mice constitutes a novel therapeutic target","volume":"177","author":"Desai","year":"2010","journal-title":"Am J Pathol"},{"key":"10.3233\/JAD-200868_ref15","first-page":"83","article-title":"Soluble amyloid beta levels are elevated in the white matter of Alzheimer\u2019s patients, independent of cortical plaque severity","volume":"17","author":"Collins-Praino","year":"2014","journal-title":"Acta Neuropathol Commun"},{"key":"10.3233\/JAD-200868_ref16","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s40478-018-0515-3","article-title":"White matter changes in Alzheimer\u2019s disease: A focus on myelin and oligodendrocytes","volume":"6","author":"Nasrabady","year":"2018","journal-title":"Acta Neuropathol Commun"},{"key":"10.3233\/JAD-200868_ref17","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1177\/0271678X15627465","article-title":"White matter hyperintensity microstructure in amyloid dysmetabolism","volume":"37","author":"Kalheim","year":"2017","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.3233\/JAD-200868_ref18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1001\/jamaneurol.2016.3232","article-title":"Association of amyloid pathology with myelin alteration in preclinical Alzheimer\u2019s disease","volume":"74","author":"Dean","year":"2017","journal-title":"JAMA Neurol"},{"key":"10.3233\/JAD-200868_ref19","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/ana.24647","article-title":"White matter hyperintensities are a core feature of Alzheimer\u2019s disease: Evidence from the dominantly inherited Alzheimer network","volume":"79","author":"Lee","year":"2016","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-200868_ref20","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1136\/jnnp-2017-316603","article-title":"CSF \u03b2-amyloid and white matter damage: A new perspective on Alzheimer\u2019s disease","volume":"89","author":"Pietroboni","year":"2018","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JAD-200868_ref21","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.neurobiolaging.2009.08.007","article-title":"Alzheimer\u2019s disease as homeostatic responses to age-related myelin breakdown","volume":"32","author":"Bartzokis","year":"2011","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-200868_ref22","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1177\/1352458516674566","article-title":"CSF \u03b2-amyloid as a putative biomarker of disease progression in multiple sclerosis","volume":"23","author":"Pietroboni","year":"2017","journal-title":"Mult Scler"},{"key":"10.3233\/JAD-200868_ref23","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/glia.440150206","article-title":"Amyloid precursor protein (APP) expression in multiple sclerosis lesions","volume":"15","author":"Gehrmann","year":"1995","journal-title":"Glia"},{"key":"10.3233\/JAD-200868_ref24","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1056\/NEJM199801293380502","article-title":"Axonal transection in the lesions of multiple sclerosis","volume":"338","author":"Trapp","year":"1998","journal-title":"N Engl J Med"},{"key":"10.3233\/JAD-200868_ref25","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1177\/1352458508100031","article-title":"Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis","volume":"15","author":"Mattsson","year":"2009","journal-title":"Mult Scler"},{"key":"10.3233\/JAD-200868_ref26","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1177\/1352458518791709","article-title":"CSF \u03b2-amyloid predicts prognosis in patients with multiple sclerosis","volume":"25","author":"Pietroboni","year":"2019","journal-title":"Mult Scler"},{"key":"10.3233\/JAD-200868_ref27","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3233\/JAD-2010-1367","article-title":"BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology","volume":"20","author":"Mulder","year":"2010","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-200868_ref28","doi-asserted-by":"crossref","first-page":"7856","DOI":"10.1523\/JNEUROSCI.3372-12.2013","article-title":"Dual cleavage of neuregulin 1 type III by BACE1 and ADAM17 liberates its EGF-like domain and allows paracrine signaling","volume":"33","author":"Fleck","year":"2013","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-200868_ref29","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S1474-4422(04)00964-0","article-title":"Biological markers in CSF and blood for axonal degeneration in multiple sclerosis","volume":"4","author":"Teunissen","year":"2005","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-200868_ref30","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.msard.2014.01.004","article-title":"Cerebrospinal fluid apolipoprotein E and phospholipid transfer protein activity are reduced in multiple sclerosis; relationships with the brain MRI and CSF lipid variables","volume":"3","author":"Vuletic","year":"2014","journal-title":"Mult Scler Relat Disord"},{"key":"10.3233\/JAD-200868_ref31","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1097\/WCO.0000000000000489","article-title":"New PET markers for the diagnosis of dementia","volume":"30","author":"Payoux","year":"2017","journal-title":"Curr Opin Neurol"},{"key":"10.3233\/JAD-200868_ref32","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/ana.22320","article-title":"Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl-11C]-2-(4- methylaminophenyl)- 6-hydroxybenzothiazole","volume":"69","author":"Stankoff","year":"2011","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-200868_ref33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3389\/fneur.2016.00053","article-title":"Amyloid proteins and their role in multiple sclerosis. Considerations in the use of amyloid-PET imaging","volume":"7","author":"Mat\u00edas-Guiu","year":"2016","journal-title":"Front Neurol"},{"key":"10.3233\/JAD-200868_ref34","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/ana.24620","article-title":"Dynamic imaging of individual remyelination. Profiles in multiple sclerosis","volume":"79","author":"Bodini","year":"2016","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-200868_ref35","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.msard.2020.101926","article-title":"Amyloid PET findings in multiple sclerosis are associated with cognitive decline at 18 months","volume":"39","author":"Pytel","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"10.3233\/JAD-200868_ref36","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s12883-015-0502-2","article-title":"Amyloid PET imaging in multiple sclerosis: An 18F-florbetaben study","volume":"15","author":"Mat\u00edas-Guiu","year":"2015","journal-title":"BMC Neurol"},{"key":"10.3233\/JAD-200868_ref37","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s00259-018-4182-1","article-title":"Amyloid PET as a marker of normal-appearing white matter early damage in multiple sclerosis: Correlation with CSF \u03b2-amyloid levels and brain volumes","volume":"46","author":"Pietroboni","year":"2019","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"10.3233\/JAD-200868_ref38","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1074\/jbc.M110.135244","article-title":"Amyloid-beta protein oligomer at low nanomolar concentrations activates microglia and induces microglial neurotoxicity","volume":"286","author":"Maezawa","year":"2011","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-200868_ref39","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/YCO.0b013e32835ed6e8","article-title":"Is Alzheimer\u2019s a disease of the white matter?","volume":"26","author":"Sachdev","year":"2013","journal-title":"Curr Opin Psychiatry"},{"key":"10.3233\/JAD-200868_ref40","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/cns.12476","article-title":"Cerebrospinal fluid A\u03b242 levels: When physiological become pathological state","volume":"21","author":"Martorana","year":"2015","journal-title":"CNS Neurosci Ther"},{"key":"10.3233\/JAD-200868_ref41","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1002\/glia.22716","article-title":"Myelination, oligodendrocytes, and serious mental illness","volume":"62","author":"Haroutunian","year":"2014","journal-title":"Glia"},{"key":"10.3233\/JAD-200868_ref42","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1001\/archneur.60.3.393","article-title":"White matter structural integrity in healthy aging adults and patients with Alzheimer disease: A magnetic resonance imaging study","volume":"60","author":"Bartzokis","year":"2003","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-200868_ref43","first-page":"1018","article-title":"Low CSF \u03b2-amyloid levels predict early regional grey matter atrophy in multiple sclerosis","volume":"39","author":"Pietroboni","year":"2019","journal-title":"Mult Scler Relat Disord"},{"key":"10.3233\/JAD-200868_ref44","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1038\/s41467-017-01150-x","article-title":"Earliest accumulation of \u03b2-amyloid occurs within the default-mode network and concurrently affects brain connectivity","volume":"8","author":"Palmqvist","year":"2017","journal-title":"Nat Commun"},{"key":"10.3233\/JAD-200868_ref45","doi-asserted-by":"crossref","first-page":"983","DOI":"10.3233\/JAD-180503","article-title":"Impaired spike timing dependent cortico-cortical plasticity in Alzheimer\u2019s disease patients","volume":"66","author":"Di Lorenzo","year":"2018","journal-title":"J Alzheimers Dis"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-200868","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:09:05Z","timestamp":1777370945000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-200868"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,27]]},"references-count":45,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3233\/jad-200868","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,27]]}}}