Gene Expression as Peripheral Biomarkers for Sporadic Alzheimer's Disease

Abstract

Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. We investigated the profiles of 33 genes, previously found by our group to have altered expression in postmortem brains of AD. The gene profiles were studied via quantitative-real-time-reverse-transcription-polymerase-chain-reaction, in whole blood samples (collected with the PAXgene blood RNA system) isolated from a population clinically diagnosed with AD and healthy controls (1-year period/ up to 4 samples). Five genes showed significant correlation to the dementia score, Mini-Mental State Examination (MMSE). Focusing on the two genes with the smallest p-value, H3-histone and cannabinoid-receptor-2, notable increases in these genes were found in peripheral blood mRNA in subjects with lower MMSE scores. Seasonal variations in gene expression were not significant due to sample size, but did seem to vary due to time of sample withdrawal. In conclusion, gene expression profiling might be a promising method to investigating a large population with the aim of developing an early diagnosis of AD.

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

“…Few animal studies which have been focused on the glutamate neurotransmission in the STZ-icv animal models revealed, in general, changes similar to those found in AD patients. An increased expression of glutamate transporter mRNA has been found previously in the STZ-icv rats (Grünblatt E et al 2004), and deficits in hippocampal synaptic transmission and long-term potentiation (LTP) observed in the STZ-icv treated rats were recently suggested to be mainly due to the postsynaptic mechanisms and were accompanied by changes in the expression and function of glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (Shonesy et al 2012). Furthermore, LTP deficits were found to correlate with decreased expression of NMDA receptor subunits NR2A and NR2B, which could be related to the reduction of brain derived neurotrophic factor (BDNF) in the STZ-icv rat model (Shonesy et al 2012).…”

RNA-Stabilized Whole Blood Samples but Not Peripheral Blood Mononuclear Cells Can Be Stored for Prolonged Time Periods Prior to Transcriptome Analysis

“…Moreover, it has been suggested that blood-based GEP can be used as a powerful tool for early diagnosis of certain solid cancer entities, [32][33][34][35][36] as well as infectious, 37,38 autoimmune, 39,40 and neurodegenerative 41 disease. Nevertheless, prospective clinical studies are still needed to validate these promising but still preliminary results in larger cohorts of patients or in individuals at risk for the respective diseases.…”

Biomarkers for Alzheimer’s disease and other forms of dementia: Clinical needs, limitations and future aspects

“…The profiling of these genes was carried our four times in a period of one year in correlation to AD and it was found that the expression of HIST1H3E was correlated in a negative 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 14 manner to the MMSE scores, while. the expression of CNR2 showed some tendency to positively correlate with the decreased MMSE score (Grunblatt et al, 2009). …”