Spatial Extent of Amyloid-β Levels and Associations With Tau-PET and Cognition

Medientyp: E-Artikel
Titel: Spatial Extent of Amyloid-β Levels and Associations With Tau-PET and Cognition
Beteiligte: Ozlen, Hazal; Pichet Binette, Alexa; Köbe, Theresa; Meyer, Pierre-François; Gonneaud, Julie; St-Onge, Frédéric; Provost, Karine; Soucy, Jean-Paul; Rosa-Neto, Pedro; Breitner, John; Poirier, Judes; Villeneuve, Sylvia; Tam, Angela; Labonte, Anne; Pichet Binette, Alexa; Faubert, Anne-Marie; Mathieu, Axel; Madjar, Cecile; Carrier, Charles Edouard; Dansereau, Christian; Kazazian, Christina; Lepage, Claude; Picard, Cynthia; Maillet, David; [...]
Erschienen: American Medical Association (AMA), 2022
Erschienen in: JAMA Neurology
Sprache: Englisch
DOI: 10.1001/jamaneurol.2022.2442
ISSN: 2168-6149
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Beschreibung: <jats:sec id="ab-noi220047-4"><jats:title>Importance</jats:title><jats:p>Preventive trials of anti-amyloid agents might preferably recruit persons showing earliest biologically relevant β-amyloid (Aβ) binding on positron emission tomography (PET).</jats:p></jats:sec><jats:sec id="ab-noi220047-5"><jats:title>Objective</jats:title><jats:p>To investigate the timing at which Aβ-PET binding starts showing associations with other markers of Alzheimer disease.</jats:p></jats:sec><jats:sec id="ab-noi220047-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>This longitudinal multicentric cohort study included 3 independent cohorts: Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) (data collected from 2012-2020), Alzheimer Disease Neuroimaging Initiative (ADNI) (data collected from 2005-2019), and Harvard Aging Brain Study (HABS) (data collected from 2011-2019). In a 3-tiered categorization of Aβ-PET binding spatial extent, individuals were assigned as having widespread Aβ deposition if they showed positive signal throughout a designated set of brain regions prone to early Aβ accumulation. Those with binding in some but not all were categorized as having regional deposition, while those who failed to show any criterion Aβ signal were considered Aβ-negative. All participants who were cognitively unimpaired at their first Aβ PET scan.</jats:p></jats:sec><jats:sec id="ab-noi220047-7"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Differences in cerebrospinal fluid (CSF), genetics, tau-PET burden, and cognitive decline.</jats:p></jats:sec><jats:sec id="ab-noi220047-8"><jats:title>Results</jats:title><jats:p>A total of 817 participants were included, including 129 from the PREVENT-AD cohort (mean [SD] age, 63.5 [4.7] years; 33 [26%] male; 126 [98%] White), 400 from ADNI (mean [SD] age, 73.6 [5.8] years; 190 [47%] male; 10 [5%] Hispanic, 338 [91%] White), and 288 from HABS (mean [SD] age, 73.7 [6.2] years; 117 [40%] male; 234 [81%] White). Compared with Aβ-negative persons, those with regional Aβ binding showed proportionately more APOE ε4 carriers (18 [64%] vs 22 [27%] in PREVENT-AD and 34 [31%] vs 38 [19%] in ADNI), reduced CSF Aβ1-42 levels (<jats:italic>F</jats:italic> = 24 and 71), and greater longitudinal Aβ-PET accumulation (significant β = 0.019 to 0.056). Participants with widespread amyloid binding further exhibited notable cognitive decline (significant β = −0.014 to −0.08), greater CSF phosphorylated tau<jats:sub>181</jats:sub> (<jats:italic>F</jats:italic> = 5 and 27), and tau-PET binding (all <jats:italic>F</jats:italic> &amp;gt; 7.55). Using each cohort’s specified dichotomous threshold for Aβ positivity or a visual read classification, most participants (56% to 100%, depending on classification method and cohort) with regional Aβ would have been classified Aβ-negative.</jats:p></jats:sec><jats:sec id="ab-noi220047-9"><jats:title>Conclusions and Relevance</jats:title><jats:p>Regional Aβ binding appears to be biologically relevant and participants at this stage remain relatively free from CSF phosphorylated tau<jats:sub>181</jats:sub>, tau-PET binding, and related cognitive decline, making them ideal targets for anti-amyloid agents. Most of these individuals would be classified as negative based on classical thresholds of Aβ positivity.</jats:p></jats:sec>

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