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Regional distribution of tau pathology in cognitively unimpaired, genetically identical twins
Author(s) -
Coomans Emma M.,
Tomassen Jori,
Wolters Emma E.,
Golla Sandeep S.V.,
den Hollander Marijke,
Verfaillie Sander C.J.,
Collij Lyduine,
Windhorst Albert D.,
Boellaard Ronald,
Barkhof Frederik,
Ossenkoppele Rik,
de Geus Eco J.C.,
Scheltens Philip,
Visser Pieter Jelle,
Van Berckel Bart N.M.,
den Braber Anouk
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045876
Subject(s) - correlation , entorhinal cortex , twin study , psychology , pathology , biology , neuroscience , medicine , genetics , hippocampus , mathematics , heritability , geometry
Background Limited information is available on the genetic and environmental contributions to early AD pathology. Within a sample of cognitively unimpaired genetically identical older twins we aimed to assess 1) effects of amyloid‐ß pathology on [ 18 F]flortaucipir (tau) binding and 2) spatial similarities in tau patterns within twin pairs. Method To date, ten twin pairs (i.e. twenty twins) from the on‐going EMIF‐AD PreclinAD study underwent dynamic (0‐30min and 80‐100min) [ 18 F]flortaucipir PET. Two twin pairs were concordant amyloid‐ß positive, four twin pairs concordant amyloid‐ß negative and four twin pairs amyloid‐ß discordant (i.e. one twin positive and co‐twin negative) based on [ 18 F]flutemetamol visual read. [ 18 F]flortaucipir binding potential (BP ND ) images were generated using receptor parametric mapping (reference region: cerebellar gray matter). First, we compared [ 18 F]flortaucipir BP ND in an early (entorhinal), intermediate (limbic) and late (neocortical) stage tau pathology region between amyloid‐ß positive and negative twins using generalized estimated equation correcting for twin dependency. Next, we examined spatial tau pattern similarities within twin pairs by correlating (Spearman) [ 18 F]flortaucipir BP ND across 46 ROIs from the Hammers template between each twin and their co‐twin for each true twin pair. Correlations were also performed for all non‐twin “random” pairs. Correlation coefficients within true twin pairs were compared to the correlation coefficients within random pairs, correcting for age and twin amyloid‐ß status. Results Amyloid‐ß positive twins showed higher [ 18 F]flortaucipir BP ND in entorhinal ( p =0.01) and limbic ( p =0.04) regions(Table‐1). Fig‐1 shows representative [ 18 F]flortaucipir images of an amyloid‐ß concordant positive, concordant negative and discordant pair , with regional similarities observed in amyloid‐ß concordant pairs as well as dissimilarities in amyloid‐ß discordant pairs (Fig‐1;Fig‐2). Between‐twin correlations across regional [ 18 F]flortaucipir BP ND , to assess spatial tau pattern similarities, were higher for true twin pairs ( r =0.71±0.17) compared to random pairs ( r =0.45±0.23) ( p =0.002)(Table‐2). Conclusion In line with previous studies, amyloid‐ß positive cognitively unimpaired twins showed higher tau deposition in early and intermediate tau stage regions. Furthermore, we observed higher spatial tau pattern similarities within true twin pairs compared to random pairs, suggesting a moderate genetic contribution to mechanisms underlying tau spread. With the upcoming larger sample we aim to further assess genetic and environmental contributions to early AD pathology.