Background: Variants in Niemann-Pick Type C genes (NPC1 and NPC2) have been suggested to play a role as risk or disease modifying factors for Alzheimer's disease (AD). Objective: The aim of this study was to analyze NPC1 and NPC2 variability in demented patients with evidence of brain amyloid-β 1-42 (Aβ) deposition and to correlate genetic data with clinical phenotypes. Methods: A targeted Next Generation Sequencing panel was customized to screen NPC1, NPC2, and main genes related to neurodegenerative dementias in a cohort of 136 demented patients with cerebrospinal fluid (CSF) low Aβ levels or positive PET with Aβ tracer and 200 non-demented geriatric subjects. Results: Seven patients were carriers of NPC variants in heterozygosis. Four of them displayed pathogenic variants previously found in NPC patients and one AD patient had a novel variant. The latter was absent in 200 non-demented elderly subjects. Five of seven patients (70%) exhibited psychiatric symptoms at onset or later as compared with 43%in non-carriers (p > 0.05). Conclusion: The frequency of NPC1 and NPC2 heterozygous variants in patients with CSF evidence of Aβ deposition is higher than in the general population.

Niemann-Pick Type C 1 (NPC1) and NPC2 gene variability in demented patients with evidence of brain amyloid deposition / Sorrentino, F.; Arighi, A.; Serpente, M.; Arosio, B.; Arcaro, M.; Visconte, C.; Rotondo, E.; Vimercati, R.; Ferri, E.; Fumagalli, G. G.; Pietroboni, A. M.; Carandini, T.; Scarpini, E.; Fenoglio, C.; Galimberti, D.. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 83:3(2021), pp. 1313-1323. [10.3233/JAD-210453]

Niemann-Pick Type C 1 (NPC1) and NPC2 gene variability in demented patients with evidence of brain amyloid deposition

Fumagalli, G. G.;
2021-01-01

Abstract

Background: Variants in Niemann-Pick Type C genes (NPC1 and NPC2) have been suggested to play a role as risk or disease modifying factors for Alzheimer's disease (AD). Objective: The aim of this study was to analyze NPC1 and NPC2 variability in demented patients with evidence of brain amyloid-β 1-42 (Aβ) deposition and to correlate genetic data with clinical phenotypes. Methods: A targeted Next Generation Sequencing panel was customized to screen NPC1, NPC2, and main genes related to neurodegenerative dementias in a cohort of 136 demented patients with cerebrospinal fluid (CSF) low Aβ levels or positive PET with Aβ tracer and 200 non-demented geriatric subjects. Results: Seven patients were carriers of NPC variants in heterozygosis. Four of them displayed pathogenic variants previously found in NPC patients and one AD patient had a novel variant. The latter was absent in 200 non-demented elderly subjects. Five of seven patients (70%) exhibited psychiatric symptoms at onset or later as compared with 43%in non-carriers (p > 0.05). Conclusion: The frequency of NPC1 and NPC2 heterozygous variants in patients with CSF evidence of Aβ deposition is higher than in the general population.
2021
3
Sorrentino, F.; Arighi, A.; Serpente, M.; Arosio, B.; Arcaro, M.; Visconte, C.; Rotondo, E.; Vimercati, R.; Ferri, E.; Fumagalli, G. G.; Pietroboni, A. M.; Carandini, T.; Scarpini, E.; Fenoglio, C.; Galimberti, D.
Niemann-Pick Type C 1 (NPC1) and NPC2 gene variability in demented patients with evidence of brain amyloid deposition / Sorrentino, F.; Arighi, A.; Serpente, M.; Arosio, B.; Arcaro, M.; Visconte, C.; Rotondo, E.; Vimercati, R.; Ferri, E.; Fumagalli, G. G.; Pietroboni, A. M.; Carandini, T.; Scarpini, E.; Fenoglio, C.; Galimberti, D.. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 83:3(2021), pp. 1313-1323. [10.3233/JAD-210453]
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