Brain Imaging and Biomarker Research Group – PI: Michael Ewers
We are interested in the detection of brain changes that underlie or modulate the manifestation of dementia symptoms in Alzheimer’s disease. The first major focus is the detection of protective brain mechanisms that delay the onset of cognitive impairment. The second focus is the development of markers for the early detection of AD. We primarily employ fMRI and DTI based analysis of functional networks along with biochemical analysis of cerebrospinal fluid markers.
Reserve and resilience in Alzheimer’s Disease
Early life-experiences such as education and higher IQ enhance reserve capacity, i.e. mitigate the impact on brain pathology on cognition in AD. Using DTI and multi-task fMRI, we map functional networks associated with protective factors. We have recently identified a highly connected hub in the frontal cortex as a key brain region underlying reserve capacity in AD (Franzmeier et al. Brain 2018). We are currently testing in longitudinal studies whether enhancing frontal hub connectivity may have a beneficial clinical impact.
We have recently founded together with Prof. Yaakov Stern (Columbia University, USA) and Prof. Gael Chetelat (INSERM, France) the professional interested area (PIA) on “Reserve, resilience and protective factors” hosted by the Alzheimer’s Association. We are currently building a consortium to collect multiple data sets for replication of neuroimaging results on reserve and thus enhance reproducibility and transparency of our findings (https://www.survio.com/survey/d/H3A1L1E8M9I3A5L1D).
Big data: Machine learning and artificial intelligence for the early diagnosis of AD
The development of markers for the prediction of AD, we are combining multi-modal imaging and biochemical markers. We use pattern recognition algorithms such as implemented in Neurominer (https://www.pronia.eu/neurominer/) to extract the best combination of markers for the prediction of cognitive decline and early diagnostic classification.
The role of TREM2-related microglia activation in Alzheimer’s
A recent focus has been centered on markers of the brain’s neuroimmune response in AD. Together with our collaborator Prof. Christian Haass (DZNE, Munich), we found changes in CSF TREM2, a marker of microglia activity, to occur up to 5 years before the onset of AD dementia in data from the international DIAN study (https://dian.wustl.edu/). Importantly, in recent studies we detected evidence supporting a protective role of TREM2 related microglia activation in AD, rendering TREM2 a potential therapeutic target.
Publications by Michael Ewers
Ewers M, Biechele G, Suárez-Calvet M, Sacher C, Blume T, Morenas-Rodriguez E, Deming Y, Piccio L, Cruchaga C, Kleinberger G, Shaw L, Trojanowski JQ, Herms J, Dichgans M; Alzheimer's Disease Neuroimaging Initiative (ADNI), Brendel M, Haass C, Franzmeier N. Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation. EMBO Mol Med. 2020 Sep 7;12(9):e12308.
Franzmeier N, Koutsouleris N, Benzinger T, Goate A, Karch CM, Fagan AM, McDade E, Duering M, Dichgans M, Levin J, Gordon BA, Lim YY, Masters CL, Rossor M, Fox NC, O'Connor A, Chhatwal J, Salloway S, Danek A, Hassenstab J, Schofield PR, Morris JC, Bateman RJ; Alzheimer's disease neuroimaging initiative (ADNI); Dominantly Inherited Alzheimer Network (DIAN), Ewers M. Predicting sporadic Alzheimer's disease progression via inherited Alzheimer's disease-informed machine-learning. Alzheimers Dement. 2020 Feb 11. [Epub ahead of print]
Ewers M, Franzmeier N, Suárez-Calvet M, Morenas-Rodriguez E, Caballero MAA, Kleinberger G, Piccio L, Cruchaga C, Deming Y, Dichgans M, Trojanowski JQ, Shaw LM, Weiner MW, Haass C; Alzheimer’s Disease Neuroimaging Initiative. Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer's disease. Sci Transl Med. 2019 Aug 28;11(507).
Franzmeier N, Ren J, Damm A, Monté-Rubio G, Boada M, Ruiz A, Ramirez A, Jessen F, Düzel E, Rodríguez Gómez O, Benzinger T, Goate A, Karch CM, Fagan AM, McDade E, Buerger K, Levin J, Duering M, Dichgans M, Suárez-Calvet M, Haass C, Gordon BA, Lim YY, Masters CL, Janowitz D, Catak C, Wolfsgruber S, Wagner M, Milz E, Moreno-Grau S, Teipel S, Grothe MJ, Kilimann I, Rossor M, Fox N, Laske C, Chhatwal J, Falkai P, Perneczky R, Lee JH, Spottke A, Boecker H, Brosseron F, Fliessbach K, Heneka MT, Nestor P, Peters O, Fuentes M, Menne F, Priller J, Spruth EJ, Franke C, Schneider A, Westerteicher C, Speck O, Wiltfang J, Bartels C, Araque Caballero MÁ, Metzger C, Bittner D, Salloway S, Danek A, Hassenstab J, Yakushev I, Schofield PR, Morris JC, Bateman RJ, Ewers M. The BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer's disease. Mol Psychiatry. 2019 Mar 21.
Perneczky R, Kempermann G, Korczyn AD, Matthews FE, Ikram MA, Scarmeas N, Chetelat G, Stern Y, Ewers M. Translational research on reserve against neurodegenerative disease: consensus report of the International Conference on Cognitive Reserve in the Dementias and the Alzheimer's Association Reserve, Resilience and Protective Factors Professional Interest Area working groups. BMC Med. 2019 Feb 27;17(1):47.
Araque Caballero MÁ, Suárez-Calvet M, Duering M, Franzmeier N, Benzinger T, Fagan AM, Bateman RJ, Jack CR, Levin J, Dichgans M, Jucker M, Karch C, Masters CL, Morris JC, Weiner M, Rossor M, Fox NC, Lee JH, Salloway S, Danek A, Goate A, Yakushev I, Hassenstab J, Schofield PR, Haass C, Ewers M. White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer's disease. Brain. 2018 Oct 1;141(10):3065-3080.
Stern Y, Arenaza-Urquijo EM, Bartrés-Faz D, Belleville S, Cantilon M, Chetelat G, Ewers M, Franzmeier N, Kempermann G, Kremen WS, Okonkwo O, Scarmeas N, Soldan A, Udeh-Momoh C, Valenzuela M, Vemuri P, Vuoksimaa E; Reserve, Resilience and Protective Factors PIA Empirical Definitions and Conceptual Frameworks Workgroup. Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimers Dement. 2018 Sep 14.
Franzmeier N, Düzel E, Jessen F, Buerger K, Levin J, Duering M, Dichgans M, Haass C, Suárez-Calvet M, Fagan AM, Paumier K, Benzinger T, Masters CL, Morris JC, Perneczky R, Janowitz D, Catak C, Wolfsgruber S, Wagner M, Teipel S, Kilimann I, Ramirez A, Rossor M, Jucker M, Chhatwal J, Spottke A, Boecker H, Brosseron F, Falkai P, Fliessbach K, Heneka MT, Laske C, Nestor P, Peters O, Fuentes M, Menne F, Priller J, Spruth EJ, Franke C, Schneider A, Kofler B, Westerteicher C, Speck O, Wiltfang J, Bartels C, Araque Caballero MÁ, Metzger C, Bittner D, Weiner M, Lee JH, Salloway S, Danek A, Goate A, Schofield PR, Bateman RJ, Ewers M. Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease. Brain. 2018 Apr 1;141(4):1186-1200.
Franzmeier N, Hartmann J, Taylor ANW, Araque-Caballero MÁ, Simon-Vermot L, Kambeitz-Ilankovic L, Bürger K, Catak C, Janowitz D, Müller C, Ertl-Wagner B, Stahl R, Dichgans M, Duering M, Ewers M. The left frontal cortex supports reserve in aging by enhancing functional network efficiency. Alzheimers Res Ther. 2018 Mar 6;10(1):28.
Ewers, Michael, Prof. Dr. / PI
Franzmeier, Nicolai, Dr. / Postdoc
Neitzel, Julia, Dr. / Postdoc
Frontzkowski, Lukas / Ph.D. student
Ren, Jinyi / Ph.D. student
Rubinski, Anna / Ph.D. student
Pietsch, Hedwig / Team assistant