Genetics and gene therapy

Members of the group

Martin Ingelsson, MD, Professor
Lars Lannfelt, MD, Professor
Vilmantas Giedraitis, PhD
Wojciech Piotr Michno, PhD
Siarhei Hladkou, PhD
Ximena Aguilar, PhD, research engineer
Sona Hakhverdyan, research assistant
Elena Katharina Witzemann, research assistant

We have access to more than 200 families with inherited forms of Alzheimer's disease (AD), frontotemporal dementia, dementia with Lewy bodies and vascular dementia. Samples from members of these families are used to study genetics of dementia disorders. We are searching for mutations within already identified disease genes and within genes not previously implicated in dementia. DNA samples from almost 400 AD patients and 300 healthy controls are being used for population-based investigations to identify genetic risk factor. For this purpose we also have access to samples from the Uppsala Longitudinal Study of Adult Men (ULSAM). We are also collaborating with genetic laboratories in Boston, Barcelona and Berlin as well as participating in a large European consortium for the study of dementia genetics, led by researchers in Lille.

Selected publications

Pagnon de la Vega M, Giedraitis V, Michno W, Kilander L, Güner G, Zielinski M, Löwenmark M, Brundin R, Danfors T, Söderberg L, Alafuzoff I, Nilsson LNG, Erlandsson A, Willbold D, Müller SA, Schröder GF, Hanrieder J, Lichtenthaler SF, Lannfelt L, Sehlin D, Ingelsson M. (2021). The Uppsala APP deletion causes early onset autosomal dominant Alzheimer's disease by altering APP processing and increasing amyloid β fibril formation. Sci Transl Med. 13: eabc6184.

Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, Boland A, Vronskaya M, van der Lee SJ, Amlie-Wolf A, Bellenguez C, Frizatti A, Chouraki V, Martin ER, Sleegers K, Badarinarayan N, Jakobsdottir J, Hamilton-Nelson KL, Moreno-Grau S, Olaso R, et al. (2019). Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat Genet. 51: 414-430.

Gyorgy B, Loov C, Zaborowski MP, Takeda S, Kleinstiver BP, Commins C, Kastanenka K, Mu D, Volak A, Giedraitis V, Lannfelt L, Maguire CA, Joung JK, Hyman BT, Breakefield XO and Ingelsson M (2018). CRISPR/Cas9 Mediated Disruption of the Swedish APP Allele as a Therapeutic Approach for Early-Onset Alzheimer's Disease. Mol Ther Nucleic Acids. 11: 429-440.

Escott-Price V, Bellenguez C, Wang LS, Choi SH, Harold D, Jones L, Holmans P, Gerrish A, Vedernikov A, Richards A, DeStefano AL, Lambert JC, Ibrahim-Verbaas CA, Naj AC, Sims R, Jun G, Bis JC, Beecham GW, Grenier-Boley B, Russo G, et al. (2014). Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease. PLoS One. 9: e94661.

Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, DeStafano AL, Bis JC, Beecham GW, Grenier-Boley B, Russo G, Thorton-Wells TA, Jones N, Smith AV, Chouraki V, Thomas C, Ikram MA, Zelenika D, Vardarajan BN, Kamatani Y, et al. (2013). Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat Genet. 45: 1452-8.

Giedraitis V, Glaser A, Sarajarvi T, Brundin R, Gunnarsson MD, Schjeide BM, Tanzi RE, Helisalmi S, Pirttila T, Kilander L, Lannfelt L, Soininen H, Bertram L, Ingelsson M and Hiltunen M (2010). CALHM1 P86L polymorphism does not alter amyloid-beta or tau in cerebrospinal fluid. Neurosci Lett. 469: 265-7.

Skoglund L, Ingvast S, Matsui T, Freeman SH, Frosch MP, Brundin R, Giedraitis V, Growdon JH, Hyman BT, Lannfelt L, Ingelsson M and Glaser A (2009). No evidence of PGRN or MAPT gene dosage alterations in a collection of patients with frontotemporal lobar degeneration. Dement Geriatr Cogn Disord. 28: 471-5.

Giedraitis V, Kilander L, Degerman-Gunnarsson M, Sundelof J, Axelsson T, Syvanen AC, Lannfelt L and Glaser A (2009). Genetic analysis of Alzheimer's disease in the Uppsala Longitudinal Study of Adult Men. Dement Geriatr Cogn Disord. 27: 59-68.

Bertram L, Schjeide BM, Hooli B, Mullin K, Hiltunen M, Soininen H, Ingelsson M, Lannfelt L, Blacker D and Tanzi RE (2008). No association between CALHM1 and Alzheimer's disease risk. Cell. 135: 993-4; author reply 994-6.