Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease

dc.creatorLopera Restrepo, Francisco Javier
dc.creatorQuiroz Gaviria, Yakeel Tatiana
dc.creatorSperling, Reisa A.
dc.creatorNorton, Daniel
dc.creatorBaena Pineda, Ana Yulied
dc.creatorArboleda Velásquez, Joseph Fitzgerald
dc.creatorCosio, Danielle
dc.creatorSchultz, Aaron
dc.creatorLapoint, Molly
dc.creatorGuzmán Vélez, Edmarie
dc.creatorMiller, John B.
dc.creatorKim, Leo A.
dc.creatorChen, Kewei
dc.creatorTariot, Pierre N.
dc.creatorReiman, Eric M.
dc.creatorJohnson, Keith A.
dc.date2022-12-25T21:11:45Z
dc.date2022-12-25T21:11:45Z
dc.date2018
dc.date.accessioned2023-08-28T20:15:25Z
dc.date.available2023-08-28T20:15:25Z
dc.identifierQuiroz YT, Sperling RA, Norton DJ, Baena A, Arboleda-Velasquez JF, Cosio D, Schultz A, Lapoint M, Guzman-Velez E, Miller JB, Kim LA, Chen K, Tariot PN, Lopera F, Reiman EM, Johnson KA. Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease. JAMA Neurol. 2018 May 1;75(5):548-556. doi: 10.1001/jamaneurol.2017.4907.
dc.identifier2168-6149
dc.identifierhttps://hdl.handle.net/10495/32980
dc.identifier10.1001/jamaneurol.2017.4907
dc.identifier2168-6157
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8476275
dc.descriptionABSTRACT: Importance It is critically important to improve our ability to diagnose and track Alzheimer disease (AD) as early as possible. Individuals with autosomal dominant forms of AD can provide clues as to which and when biological changes are reliably present prior to the onset of clinical symptoms. Objective: To characterize the associations between amyloid and tau deposits in the brains of cognitively unimpaired and impaired carriers of presenilin 1 (PSEN1) E280A mutation. Design, Setting, and Participants: In this cross-sectional imaging study, we leveraged data from a homogeneous autosomal dominant AD kindred, which allowed us to examine measurable tau deposition as a function of individuals’ proximity to the expected onset of dementia. Cross-sectional measures of carbon 11–labeled Pittsburgh Compound B positron emission tomography (PET) and flortaucipir F 18 (previously known as AV 1451, T807) PET imaging were assessed in 24 PSEN1 E280A kindred members (age range, 28-55 years), including 12 carriers, 9 of whom were cognitively unimpaired and 3 of whom had mild cognitive impairment, and 12 cognitively unimpaired noncarriers. Main Outcomes and Measures: We compared carbon 11–labeled Pittsburgh Compound B PET cerebral with cerebellar distribution volume ratios as well as flortaucipir F 18 PET cerebral with cerebellar standardized uptake value ratios in mutation carriers and noncarriers. Spearman correlations characterized the associations between age and mean cortical Pittsburgh Compound B distribution volume ratio levels or regional flortaucipir standardized uptake value ratio levels in both groups. Results: Of the 24 individuals, the mean (SD) age was 38.0 (7.4) years, or approximately 6 years younger than the expected onset of clinical symptoms in carriers. Compared with noncarriers, cognitively unimpaired mutation carriers had elevated mean cortical Pittsburgh Compound B distribution volume ratio levels in their late 20s, and 7 of 9 carriers older than 30 years reached the threshold for amyloidosis (distribution volume ratio level > 1.2). Elevated levels of tau deposition were seen within medial temporal lobe regions in amyloid-positive mutation carriers 6 years before clinical onset of AD in this kindred. Substantial tau deposition in the neocortex was only observed in 1 unimpaired carrier and in those with mild cognitive impairment. β-Amyloid uptake levels were diffusely elevated in unimpaired carriers approximately 15 years prior to expected onset of mild cognitive impairment. In carriers, higher levels of tau deposition were associated with worse performance on the Mini-Mental State Examination (entorhinal cortex: r = −0.60; P = .04; inferior temporal lobe: r = −0.54; P = .06) and the Consortium to Establish a Registry for Alzheimer Disease Word List Delayed Recall (entorhinal cortex: r = −0.86; P < .001; inferior temporal lobe: r = −0.70; P = .01). Conclusions and Relevance: The present findings add to the growing evidence that molecular markers can characterize biological changes associated with AD in individuals who are still cognitively unimpaired. The findings also suggest that tau PET imaging may be useful as a biomarker to distinguish individuals at high risk to develop the clinical symptoms of AD and to track disease progression.
dc.descriptionCOL0010744
dc.descriptionCOL0007551
dc.format9
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Medical Association
dc.publisherGrupo de Neurociencias de Antioquia
dc.publisherGrupo Neuropsicología y Conducta
dc.publisherChicago, Estados Unidos
dc.relationJAMA Neurol.
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/2.5/co/
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectMental Status and Dementia Tests
dc.subjectFactores de Edad
dc.subjectAge Factors
dc.subjectEnfermedad de Alzheimer
dc.subjectAlzheimer Disease
dc.subjectAmiloide
dc.subjectAmyloid
dc.subjectCompuestos de Anilina - farmacocinética
dc.subjectAniline Compounds - pharmacokinetics
dc.subjectEncéfalo
dc.subjectBrain
dc.subjectTrastornos del Conocimiento
dc.subjectCognition Disorders
dc.subjectProteínas tau
dc.subjecttau Proteins
dc.subjecthttp://id.nlm.nih.gov/mesh/D000073216
dc.titleAssociation Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typehttp://purl.org/coar/resource_type/c_2df8fbb1
dc.typehttps://purl.org/redcol/resource_type/ART
dc.typeArtículo de investigación


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