- Meeting abstract
- Open Access
Multidimensional evaluation in clinical diagnosis of Alzheimer’s disease: genetic risk in Alzheimer’s disease and neurodegenerative dementias
BMC Geriatrics volume 10, Article number: A90 (2010)
Late onset degenerative dementia is a growing, common and complex disorder in which the aetiological role played by environment and genes has not yet been established. A familial component is frequently ascertained in Alzheimer’s disease (AD) (30% of first degree relatives affected) and also in Frontotemporal Dementia (FTD) (40-60%).
Early onset degenerative dementia has sometimes been recognized as caused by autosomal dominant genes, Presenilines (PS1 and PS2) and the Amyloid Precursor Protein (APP) in AD, whereas in Frontotemporal dementia, two major genes (Microtubule Associated Protein tau, MAPT and Progranulin, PGRN) have also been identified.
PS1 and MAPT mutations have been identified also in in very early onset patients (PS1 24 years , MAPT 22 years ), but also in late onset patients (PS1 78 years , MAPT 75 years  87 years .
To evaluate whether FAD and PGRN gene mutations account for late onset dementia.
Materials and methods
Late onset familial dementia patients (onset >65 years) were regularly diagnosed in our centre.
Diagnosis of dementia was performed through a detailed clinical assessment. The NINCDS-ADRDA and Lund-Manchester group criteria were used for diagnosis of AD and FTD respectively.
Molecular screening of PS1, PS2, APP and PGRN genes was performed.
Three more unrelated cases with an APP A713T mutation showed an onset age between 73 and 82 years . A novel PGRN c1145insA has been identified in a FTD patient of 87 years belonging to a pedigree whose age at onset spans from 35 to 87 .
Several autosomal dominant genes, either in AD or in FTD show an impact on late onset dementia. Heritability in late onset forms is now more evident, probably due to longer life survival. It is possible that mutation frequency has been underestimated due to the lack of wide genetic epidemiology. Genetic screening of FAD and PGRN genes might be recommended in familial late onset dementia as a part of Multidimensional evaluation.
Wisniewski T, Dowjat WK, Buxbaum JD, Khorkova O, Efthimiopoulos S, Kulczycki J, et al: A novel Polish presenilin-1 mutation (P117L) is associated with familial Alzheimer's disease and leads to death as early as the age of 28 years. Neuroreport. 1998, 9 (2): 217-221. 10.1097/00001756-199801260-00008.
Cruts M, van Duijn CM, Backhovens H, Van den Broeck M, Wehnert A, Serneels S, et al: Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. Hum Mol Genet. 1998, 7 (1): 43-51. 10.1093/hmg/7.1.43.
Neumann M, Diekmann S, Bertsch U, Vanmassenhove B, Bogerts B, Kretzschmar HA: Novel G335V mutation in the tau gene associated with early onset familial frontotemporal dementia. Neurogenetics. 2005, 6: 91-95. 10.1007/s10048-005-0210-y.
Hayashi S, Toyoshima Y, Hasegawa M, Umeda Y, Wakabayashi K, Tokiguchi S, et al: Late-onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation. Annals of Neurology. 2002, 51: 525-530. 10.1002/ana.10163.
Bruni AC, Momeni P, Bernardi L, Tomaino C, Frangipane F, Elder J, et al: Heterogeneity within a large kindred with frontotemporal dementia: a novel progranulin mutation. Neurology. 2007, 69 (2): 140-147. 10.1212/01.wnl.0000265220.64396.b4.
Tomaino C, Bernardi L, Anfossi M, Costanzo A, Ferrise F, Gallo M, et al: Presenilin 2 Ser130Leu mutation in a case of late-onset "sporadic" Alzheimer's disease. J Neurol. 2007, 254 (3): 391-393. 10.1007/s00415-006-0373-y.
Bernardi L, Tomaino C, Anfossi M, Gallo M, Geracitano S, Puccio G, et al: Late onset familial Alzheimer's disease: novel presenilin 2 mutation and PS1 E318G polymorphism. J Neurol. 2008, 255 (4): 604-606. 10.1007/s00415-008-0764-3.
Bernardi L, Geracitano S, Colao R, Puccio G, Gallo M, Anfossi M, et al: AbetaPP A713T Mutation in Late Onset Alzheimer's Disease with Cerebrovascular Lesions. J Alzheimers Dis. 2009, [Epub ahead of print]
About this article
Cite this article
Bruni, A.C. Multidimensional evaluation in clinical diagnosis of Alzheimer’s disease: genetic risk in Alzheimer’s disease and neurodegenerative dementias. BMC Geriatr 10, A90 (2010) doi:10.1186/1471-2318-10-S1-A90
- Amyloid Precursor Protein
- Frontotemporal Dementia
- Late Onset Patient
- MAPT Mutation