Guerini Franca Rosa, Farina Elisabetta, Costa Andrea Saul, Baglio Francesca, Saibene Francesca Lea, Margaritella Nicolò, Calabrese Elena, Zanzottera Milena, Bolognesi Elisabetta, Nemni Raffaello, Clerici Mario
Don C. Gnocchi Foundation IRCCS, Milan, Italy fguerini@dongnocchi.
Don C. Gnocchi Foundation IRCCS, Milan, Italy.
Neurorehabil Neural Repair. 2016 Oct;30(9):883-93. doi: 10.1177/1545968316642523. Epub 2016 Apr 13.
Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder. Rate of decline and functional restoration in AD greatly depend on the capacity for neural plasticity within residual neural tissues; this is at least partially influenced by polymorphisms in genes that determine neural plasticity, including Apolipoprotein E4 (ApoE4) and synaptosomal-associated protein of 25 kDa (SNAP-25).
We investigated whether correlations could be detected between polymorphisms of ApoE4 and SNAP-25 and the outcome of a multidimensional rehabilitative approach, based on cognitive stimulation, behavioral, and functional therapy (multidimensional stimulation therapy [MST]).
Fifty-eight individuals with mild-to-moderate AD underwent MST for 10 weeks. Neuro-psychological functional and behavioral evaluations were performed blindly by a neuropsychologist at baseline and after 10 weeks of therapy using Mini-Mental State Examination (MMSE), Functional Living Skill Assessment (FLSA), and Neuropsychiatric Inventory (NPI) scales. Molecular genotyping of ApoE4 and SNAP-25 rs363050, rs363039, rs363043 was performed. Results were correlated with ΔMMSE, ΔNPI and ΔFLSA scores by multinomial logistic regression analysis.
Polymorphisms in both genes correlated with the outcome of MST for MMSE and NPI scores. Thus, higher overall MMSE scores after rehabilitation were detected in ApoE4 negative compared to ApoE4 positive patients, whereas the SNAP-25 rs363050(G) and rs363039(A) alleles correlated with significant improvements in behavioural parameters.
Polymorphisms in genes known to modulate neural plasticity might predict the outcome of a multistructured rehabilitation protocol in patients with AD. These data, although needing confirmation on larger case studies, could help optimizing the clinical management of individuals with AD, for example defining a more intensive treatment in those subjects with a lower likelihood of success.
阿尔茨海默病（AD）是一种高度流行的神经退行性疾病。AD的衰退率和功能恢复很大程度上取决于残余神经组织内神经可塑性的能力；这至少部分受到决定神经可塑性的基因多态性的影响，包括载脂蛋白E4（ApoE4）和25 kDa突触体相关蛋白（SNAP - 25）。
我们研究了基于认知刺激、行为和功能治疗（多维刺激疗法[MST]）的多维康复方法的结果与ApoE4和SNAP - 25基因多态性之间是否存在相关性。
58名轻度至中度AD患者接受了为期10周的MST。在基线时以及治疗10周后，由一名神经心理学家使用简易精神状态检查表（MMSE）、功能生活技能评估（FLSA）和神经精神科问卷（NPI）量表对神经心理功能和行为进行盲法评估。对ApoE4和SNAP - 25的rs363050、rs363039、rs363043进行分子基因分型。通过多项逻辑回归分析将结果与ΔMMSE、ΔNPI和ΔFLSA评分相关联。
两个基因的多态性均与MST治疗MMSE和NPI评分的结果相关。因此，与ApoE4阳性患者相比，ApoE4阴性患者康复后总体MMSE评分更高，而SNAP - 25的rs363050（G）和rs363039（A）等位基因与行为参数的显著改善相关。
已知调节神经可塑性的基因多态性可能预测AD患者多结构康复方案的结果。这些数据虽然需要在更大规模的病例研究中得到证实，但可能有助于优化AD患者的临床管理，例如为成功可能性较低的患者确定更强化的治疗方案。
