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SIR – Alzheimer's disease (AD) is a chronic brain disorder associated with specific pathological changes resulting in neurodegeneration and in progressive development of dementia. This disease is clinically characterized by memory, reasoning and speech disorders and pathologically by the presence of senile plaques (SP), neurofibrillary tangles, and loss of syn-apses. 1 There are various hypotheses regarding an involvement of genetic factors in the development of AD. Mutations of genes encoding amyloid precursor protein, presenilin-1 and presenilin-2 cause familial AD, 2,3 and the ⑀4 allele of apolipoprotein E (APOE) gene gives susceptibility to familial and sporadic AD. 4 However, this genetic marker cannot explain the overall genetic susceptibility and additional/other genes may be involved in the development of AD. Genes involved in the neurodevelopmental process may be considered good candidates to confer susceptibility to AD. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors which promotes survival, differentiation and maintenance of neurons in peripheral and central nervous system during normal development, 5 influences axonal growth and connectivity 6 and participates in the local responses to various types of neuronal stress or insults. 7 Table 1 Allele and genotype frequencies of the BDNF gene polymorphism at position 196 in Alzheimer patients and controls Alzheimer patients (n = 130) Healthy volunteers (n = 111) BDNF allele frequency Several lines of evidence have suggested altered functions of this gene in the pathogenesis of neurodeg-enerative diseases including Alzheimer's disease: reduced levels of BDNF mRNA in the hippocampus, in the temporal cortex, in brain homogenates and in frontal cortex neurons have been found in individuals with AD. 8 In order to verify a potential role of the BDNF gene in the neuropathogenesis of Alzheimer's disease, we analyzed allelic distribution of a polymorphism in the coding region of the BDNF gene in a diagnosed AD sample and in a control group. The polymorphism studied is a A/G (Met/Val) substitution located in the propeptide region, a highly unstable region constituted by 110 aa, in the BDNF gene at position 196 (codon 66) (SWISS.PROT: P23560.VAR 004626). Genomic DNA was extracted from blood samples obtained, after informed consent, from 130 Alzheimer's patients (mean age 72 ± 3 years; 90 women and 40 men) recruited at the Alzheimer Unit of IRCCS-Fatebenefrat-elli (Brescia, Italy) and 111 healthy ethnically and age-matched volunteers. Patients and controls were Cauca-sians living in Northern Italy. Genotyping for this polymorphism has been done …

Association between the BDNF 196 A/G polymorphism and sporadic Alzheimer's disease