|dc.description.abstract||International healthcare organizations, public services, social bodies, doctors, and general people worldwide have increasingly concerned on global trends in the projection to increase of aging populations. Many aspects including demographic and epidemiologic transitions, increasing medical and social costs related to aging, and the implications for public health is needed to explore. Apart from overall health, and socioeconomic aspects relate to unemployed elderly individuals, neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (PD) have come to the main stage of the global concern, which their therapies will be a major community problem in term of the needs of the development of effective medications, the improvement of healthcare and rehabilitation, and the ability to increase the numbers of healthcare workers. Furthermore, an increased expense for those needs is likely to ask from each national social service. The strategy of prevention of neurodegenerative diseases is theoretically the best way to reduce the cost for caring the elderly as all of you can imagine how expensive the cost of those treatments can be.
At the beginning of the symptomatic stage of neurodegenerative diseases, affected nervous system has already lost a significant numbers of neurons. Thus the effective neuroprotective therapy should generally be introduced before the symptomatic stage of those diseases. Specific biomarkers are therefore necessary for early diagnoses and commencing of the neuroprotective therapy. Here, we demonstrate the example of our work on PD in order to develop specific biomarker for Thais.
PD is the second most common neurodegenerative diseases. Both environmental and genetic factors are important risks of developing PD. Several genetic variants in various human genes have been identified to be genetic causes and risk variants of PD. We intensively analyzed leucine-rich repeat kinase 2 (LRRK2), glucocerebrosidase (GBA1) and parkin genes in a large Thai cohort of 492 PD patients and 480 elderly control subjects without parkinsonism. Regarding LRRK2, R1628P was the commonest risk variant (11% in PD vs. 6% in controls; Odds ratio= 1.81, 95%CI=1.10-2.97). However, G2385R and G2019S, the 2 major risk variants in Chinese, Japanese, Caucasians and African-Arabs, were rare in Thais (<0.5, 0%,respectively). This data implies that Certain LRRK2 variants appear to be generally distributed among East Asians, however, in widely different frequencies. The PD patients carrying p.R1628P had earlier age at onset (56±13 vs 60±12; P=0.021) and a more rapidly progressive course (P<0.001) than the patients carrying wild-type nucleotide.
Regarding GBA1 analysis, the study identified 6 heterozygous point mutations (4 were novel) in 24 PD patients (5%). Additional analysis of the family pedigrees suggested that 2 patients possibly transmitted by autosomal dominant fashion with age-dependent penetrance. Multiple logistic regression analysis revealed that GBA mutations were more frequent in early-onset PD (age at onset≤50 years) than late-onset PD groups (OR=4.64, P<0.022). Patients with GBA mutations had mean age at onset (43.1±10.2) earlier than patients without GBA mutations (54.4±13.9, P=0.002). The patients with GBA mutations also had a more rapid progressive course, in which they were more likely to have higher Hoehn and Yahr staging (OR=4.20, P=0.006) and slightly lower means of Schwab-England ADL score [74.1±17.1 vs 81.0±18.08 (OR=0.98, 95%CI=0.96-1.01, P=0.162)].
For parkin analysis, we identified exon deletions in 9 patients and point mutations in 11 patients (4%) mainly on early-onset PD. In summary, the total of over 18% in our large Thai PD cohort has significant genetic predisposing factors susceptible to develop PD. Further study on all known susceptible genes (over 10 genes) would gain insight on genetic risks related to PD, which it in turn will help in developing an effective biomarker for PD in the future.||en_US