TY - JOUR
T1 - Role of neurodevelopment involved genes in psychiatric comorbidities and modulation of inflammatory processes in Alzheimer's disease
AU - Stefano, Porcelli
AU - Concetta, Crisafulli
AU - Luigi, Donato
AU - Marco, Calabrò
AU - Antonis, Politis
AU - Ioannis, Liappas
AU - Diego, Albani
AU - Anna Rita, Atti
AU - Raffaele, Salfi
AU - Ilaria, Raimondi
AU - Gianluigi, Forloni
AU - George N., Papadimitriou
AU - Diana, De Ronchi
AU - Alessandro, Serretti
N1 - Funding Information:
The research at Istituto di Ricerche Farmacologiche “Mario Negri” was supported by Fondazione Italo Monzino, Milan, Italy . We thank Manuel Mayhaus for technical help with the Sequenom platform.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/11/15
Y1 - 2016/11/15
N2 - Introduction With the increase of the population's average age, Alzheimer's disease (AD) is becoming one of the most disabling diseases worldwide. Recently, neurodevelopment processes have been involved in the AD etiopathogenesis. Genetic studies in this field could contribute to our knowledge and suggest new molecular targets for possible treatments. Methods Our primary aim was to investigate the associations among single nucleotide polymorphisms (SNPs) within neurodevelopment related genes (BDNF, ST8SIA2, C15orf32, NCAPG2, ESYT2, WDR60, LOC154822, VIPR2, GSK3B, NR1I2, ZNF804A, SP4) and AD. A number of exploratory analyses was also performed to evaluate the associations with the presence of behavioral and psychiatric symptoms of dementia (BPSD), as well as with variations in hematological parameters. Two independent samples were investigated, one of 228 Greek subjects and one sample of 229 Italian subjects, including 156 Alzheimer's Disease patients CE patients and 301 healthy controls. All patients were affected by late onset AD (LOAD). Results None of the analyzed SNPs was associated with AD in our samples. In the exploratory analyses, several genetic variants were associated with inflammation parameters in the Greek sample and in the merged one, suggesting a relationship among these genes and the modulation of inflammation and the immune response. Other exploratory analyses showed associations among several SNPs and psychiatric symptomatology in the Greek sample, suggesting a possible modulation of these variants on psychiatric comorbidities in AD. Conclusions Although we failed to find a direct relationship between AD and the genetic variants investigated, possible connections with inflammation and psychiatric symptoms were suggested.
AB - Introduction With the increase of the population's average age, Alzheimer's disease (AD) is becoming one of the most disabling diseases worldwide. Recently, neurodevelopment processes have been involved in the AD etiopathogenesis. Genetic studies in this field could contribute to our knowledge and suggest new molecular targets for possible treatments. Methods Our primary aim was to investigate the associations among single nucleotide polymorphisms (SNPs) within neurodevelopment related genes (BDNF, ST8SIA2, C15orf32, NCAPG2, ESYT2, WDR60, LOC154822, VIPR2, GSK3B, NR1I2, ZNF804A, SP4) and AD. A number of exploratory analyses was also performed to evaluate the associations with the presence of behavioral and psychiatric symptoms of dementia (BPSD), as well as with variations in hematological parameters. Two independent samples were investigated, one of 228 Greek subjects and one sample of 229 Italian subjects, including 156 Alzheimer's Disease patients CE patients and 301 healthy controls. All patients were affected by late onset AD (LOAD). Results None of the analyzed SNPs was associated with AD in our samples. In the exploratory analyses, several genetic variants were associated with inflammation parameters in the Greek sample and in the merged one, suggesting a relationship among these genes and the modulation of inflammation and the immune response. Other exploratory analyses showed associations among several SNPs and psychiatric symptomatology in the Greek sample, suggesting a possible modulation of these variants on psychiatric comorbidities in AD. Conclusions Although we failed to find a direct relationship between AD and the genetic variants investigated, possible connections with inflammation and psychiatric symptoms were suggested.
KW - Alzheimer's disease
KW - Depression
KW - Genetics
KW - Inflammation
KW - Neurodevelopment
KW - Psychosis
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U2 - 10.1016/j.jns.2016.09.053
DO - 10.1016/j.jns.2016.09.053
M3 - Article
C2 - 27772752
AN - SCOPUS:84989223368
VL - 370
SP - 162
EP - 166
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
ER -