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Neurodegenerative diseases: complexity of clinical phenotypes in genetic models of alzheimer’s disease and frontotemporal dementia
BMC Geriatrics volume 10, Article number: A89 (2010)
Neurodegenerative diseases are a wide and complex group of disorders, age – associated, chronic and progressive whith unknown, and probably different, aetiologies. The complexity of the phenotype is probably due to the expression of a selective vulnerability of the different neuronal population and to the different pathogenetic mechanisms. This aetiopathogenetic complexity has been approached through the study of simple models constituted by the large Calabrian families in which Alzheimer’s disease (AD) segregates associated to the Presenilin 1 (PS1) Met 146Leu mutation  and Frontotemporal dementia (FTD) is caused by the Progranulin (GRN) c1145insA mutation .
To investigate the phenotypic variability at onset in patients belonging to the two families for which all data (demographic, clinical and genetic) were available.
Materials and methods
The clinical presentations were studied in 50 out of 148 familial AD (FAD) patients (age at onset = 4 0.0±4.8; 38% women, 18 alive) and in 9 out of 34 patients (age at onset 65.1±17.1) belonging to the FTD family.
Phenotypic variability at onset in AD is broad: four different clinical presentations may be recognized: 1) Amnestic (38%); 2) Disoriented (20%); 3) Dysexecutive (14%); 4) Apathetic (28 %). In the FTD, 89% of patients presented at onset with a memory deficit and 33% were spatially disoriented.
The study conducted on AD and FTD genetic models provides evidence that different genotypes present with a clinical overlapping at onset: symptoms classically associated with FTD are also present in AD and, conversely, FTD patients who are carriers of a PGRN mutation always show a memory deficit. Knowledge advancement calls for a steady upgrade and revision of the clinical criteria routinely used in the diagnostic processing.
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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.
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Cite this article
Bruni, A.C. Neurodegenerative diseases: complexity of clinical phenotypes in genetic models of alzheimer’s disease and frontotemporal dementia. BMC Geriatr 10, A89 (2010). https://doi.org/10.1186/1471-2318-10-S1-A89
- Neurodegenerative Disease
- Genetic Model
- Clinical Phenotype
- Memory Deficit