OBJECTIVE: To determine the rate of tau accumulation in healthy older adults (OA) and patients with Alzheimer disease (AD), as well as the relationship of tau accumulation to cortical atrophy. METHODS: Two longitudinal flortaucipir (FTP) positron emission tomography (PET) and magnetic resonance imaging (MRI) scans were acquired from 42 OA (21 Pittsburg compound B [PiB]+ , age = 77.6 ± 4.6 years, 25 female [F]/17 male [M]) and 19 PiB+ patients with AD (age = 63.1 ± 10.3 years, 12 F/7 M) over 1 to 3 years of follow-up. FTP change, structural MRI measures of atrophy, and cross-modal correlations were examined on a voxelwise level. Regional annual percentage change in FTP was also calculated. RESULTS: Voxelwise FTP change in AD showed the greatest increases in lateral and medial frontal lobes. Atrophy over the same interval was more widespread and included posteromedial cortical areas, where tau accumulation rates were lower. In OA, FTP binding increased in bilateral temporal lobe and retrosplenial cortex, accompanied by atrophy in the same regions. There were no associations between voxelwise change in FTP and sex, PiB, or APOE. Regional FTP significantly increased at follow-up in OA and patients with AD. Mixed effects models showed greater FTP increases in AD compared to OA, and no differences within OA based on PiB status. INTERPRETATION: Our findings indicate that tau accumulates even in amyloid-negative healthy OA and this process can be measured with in vivo tau-PET. In OA, tau accumulation and atrophy share a similar topography. In AD, tau increases more rapidly and accumulation occurs in frontal regions that are not yet undergoing significant atrophy. Ann Neurol 2019; 1-12 ANN NEUROL 2019;85:229-240.
OBJECTIVE: To determine the rate of tau accumulation in healthy older adults (OA) and patients with Alzheimer disease (AD), as well as the relationship of tau accumulation to cortical atrophy. METHODS: Two longitudinal flortaucipir (FTP) positron emission tomography (PET) and magnetic resonance imaging (MRI) scans were acquired from 42 OA (21 Pittsburg compound B [PiB]+ , age = 77.6 ± 4.6 years, 25 female [F]/17 male [M]) and 19 PiB+ patients with AD (age = 63.1 ± 10.3 years, 12 F/7 M) over 1 to 3 years of follow-up. FTP change, structural MRI measures of atrophy, and cross-modal correlations were examined on a voxelwise level. Regional annual percentage change in FTP was also calculated. RESULTS: Voxelwise FTP change in AD showed the greatest increases in lateral and medial frontal lobes. Atrophy over the same interval was more widespread and included posteromedial cortical areas, where tau accumulation rates were lower. In OA, FTP binding increased in bilateral temporal lobe and retrosplenial cortex, accompanied by atrophy in the same regions. There were no associations between voxelwise change in FTP and sex, PiB, or APOE. Regional FTP significantly increased at follow-up in OA and patients with AD. Mixed effects models showed greater FTP increases in AD compared to OA, and no differences within OA based on PiB status. INTERPRETATION: Our findings indicate that tau accumulates even in amyloid-negative healthy OA and this process can be measured with in vivo tau-PET. In OA, tau accumulation and atrophy share a similar topography. In AD, tau increases more rapidly and accumulation occurs in frontal regions that are not yet undergoing significant atrophy. Ann Neurol 2019; 1-12 ANN NEUROL 2019;85:229-240.
Authors: Jerod M Rasmussen; Anita Lakatos; Theo G M van Erp; Frithjof Kruggel; David B Keator; James T Fallon; Fabio Macciardi; Steven G Potkin Journal: Biochim Biophys Acta Date: 2011-09-19
Authors: M L Gorno-Tempini; A E Hillis; S Weintraub; A Kertesz; M Mendez; S F Cappa; J M Ogar; J D Rohrer; S Black; B F Boeve; F Manes; N F Dronkers; R Vandenberghe; K Rascovsky; K Patterson; B L Miller; D S Knopman; J R Hodges; M M Mesulam; M Grossman Journal: Neurology Date: 2011-02-16 Impact factor: 9.910
Authors: Samuel N Lockhart; Nagehan Ayakta; Joseph R Winer; Renaud La Joie; Gil D Rabinovici; William J Jagust Journal: Neurology Date: 2017-02-10 Impact factor: 9.910
Authors: Adam J Schwarz; Peng Yu; Bradley B Miller; Sergey Shcherbinin; James Dickson; Michael Navitsky; Abhinay D Joshi; Michael D Devous; Mark S Mintun Journal: Brain Date: 2016-03-02 Impact factor: 13.501
Authors: Michael Schöll; Samuel N Lockhart; Daniel R Schonhaut; James P O'Neil; Mustafa Janabi; Rik Ossenkoppele; Suzanne L Baker; Jacob W Vogel; Jamie Faria; Henry D Schwimmer; Gil D Rabinovici; William J Jagust Journal: Neuron Date: 2016-03-02 Impact factor: 17.173
Authors: Chester A Mathis; Yanming Wang; Daniel P Holt; Guo-Feng Huang; Manik L Debnath; William E Klunk Journal: J Med Chem Date: 2003-06-19 Impact factor: 7.446
Authors: Irene Sintini; Jonathan Graff-Radford; Matthew L Senjem; Christopher G Schwarz; Mary M Machulda; Peter R Martin; David T Jones; Bradley F Boeve; David S Knopman; Kejal Kantarci; Ronald C Petersen; Clifford R Jack; Val J Lowe; Keith A Josephs; Jennifer L Whitwell Journal: Brain Date: 2020-07-01 Impact factor: 13.501
Authors: Daniel Albrecht; A Lisette Isenberg; Joy Stradford; Teresa Monreal; Abhay Sagare; Maricarmen Pachicano; Melanie Sweeney; Arthur Toga; Berislav Zlokovic; Helena Chui; Elizabeth Joe; Lon Schneider; Peter Conti; Kay Jann; Judy Pa Journal: J Neurosci Date: 2020-10-12 Impact factor: 6.167
Authors: Matthew R Scott; Olivia L Hampton; Rachel F Buckley; Jasmeer P Chhatwal; Bernard J Hanseeuw; Heidi Il Jacobs; Michael J Properzi; Justin S Sanchez; Keith A Johnson; Reisa A Sperling; Aaron P Schultz Journal: Neuroimage Date: 2020-06-05 Impact factor: 6.556
Authors: Rene L Utianski; Peter R Martin; Hugo Botha; Christopher G Schwarz; Joseph R Duffy; Ronald C Petersen; David S Knopman; Heather M Clark; Alissa M Butts; Mary M Machulda; Clifford R Jack; Val J Lowe; Jennifer L Whitwell; Keith A Josephs Journal: Cortex Date: 2019-11-19 Impact factor: 4.027
Authors: Renaud La Joie; Adrienne V Visani; Suzanne L Baker; Jesse A Brown; Viktoriya Bourakova; Jungho Cha; Kiran Chaudhary; Lauren Edwards; Leonardo Iaccarino; Mustafa Janabi; Orit H Lesman-Segev; Zachary A Miller; David C Perry; James P O'Neil; Julie Pham; Julio C Rojas; Howard J Rosen; William W Seeley; Richard M Tsai; Bruce L Miller; William J Jagust; Gil D Rabinovici Journal: Sci Transl Med Date: 2020-01-01 Impact factor: 17.956
Authors: Diana Younan; Andrew J Petkus; Keith F Widaman; Xinhui Wang; Ramon Casanova; Mark A Espeland; Margaret Gatz; Victor W Henderson; JoAnn E Manson; Stephen R Rapp; Bonnie C Sachs; Marc L Serre; Sarah A Gaussoin; Ryan Barnard; Santiago Saldana; William Vizuete; Daniel P Beavers; Joel A Salinas; Helena C Chui; Susan M Resnick; Sally A Shumaker; Jiu-Chiuan Chen Journal: Brain Date: 2020-01-01 Impact factor: 13.501