IP‐10 serum levels are not increased in mild cognitive impairment and Alzheimer's disease

Interferon-c-inducible protein-10 (IP-10) levels were increased in cerebrospinal fluid (CSF) from patients with mild but not severe Alzheimer’s disease(AD), as well as in subjects with amnestic mild cognitive impairment (MCI) [1,2]. No investigation have been so far carried out in the serum from AD patients, despite a growing body of evidence supporting the hypothesis that some peripheral modifications occur very early during the pathogenesis of the disease [3] implying a potential usefulness as biomarkers for early diagnosis and disease progression. Forty-eight Italian AD patients as well as 36 subjects with MCI were consecutively recruited at Alzheimer Units of Ospedale Maggiore Policlinico and Ospedale L. Sacco, Milan. All patients underwent a standard battery of examinations, including medical history, physical and neurological examination, screening laboratory tests, neurocognitive evaluation and brain magnetic resonance imaging. The diagnosis of probable AD was made according to National Institute of Neurological and Communicative Disorders and Stroke, and Alzheimer’s Disease and Related Disorders criteria. MCI diagnosis was made in accordance with Petersen et al. s clinical criteria [4]. The control group consisted of 29 healthy nondemented [Mini Mental State Examination (MMSE): 28–30] volunteers matched for ethnic background and age. Both patients and controls didn’t have chronic infections, diabetes or vascular disorders (Hachinski Ischaemic Score £4). An informed consent to participate in this study was given by all individuals; in six cases of severe dementia (MMSE < 14) the consent was given by the caregiver. All subjects were genotyped for the apolipoprotein E (ApoE) status (Table 1). Interferon-c-inducible protein-10 serum levels were measured with specific enzymelinked immunosorbent assay (R&D systems, Minneapolis, MN, USA). Total RNA from peripheral blood mononuclear cells (PBMC) of six subjects for each group was extracted, reverse-transcribed and quantified using the TaqMan technique. No significant differences in serum median IP-10 levels were found in MCI or AD compared with healthy subjects (120.6 and 108.0 pg/ml vs. 103.2 pg/ml, respectively, P 1⁄4 0.073), even stratifying patients according to gender or to the presence of ApoE e4 allele. No correlation between IP-10 levels and MMSE scores or the duration of the disease was found, whereas a significant correlation with age was observed in the overall population analysed (Spearman test: q 1⁄4 0.21, P 1⁄4 0.026). Similarly, a trend towards an increase of IP-10 PBMC mRNA levels with ageing was observed (q 1⁄4 0.36, P 1⁄4 0.096). ApoE e4 allele frequency was significantly increased in AD as compared with controls [39.6% vs. 13.8%, P 1⁄4 0.02, odds ratio (OR): 2.87, 95% confidence interval (CI): 1.29–12.95]. In MCI group, e4 allele frequency was higher than controls, although not to a significant extent (22.2%, P > 0.05). After a 1to 2-year follow up, 11 MCI developed AD. Five of them were e4 carriers. According to these results, IP-10 serum levels are not increased in AD andMCI. A previous study demonstrated an increase of IP-10 in CSF [1,2], thus this modification is probably to reflect a process occurring specifically in the brain, and doesn’t influence peripheral levels. IP-10 serum levels seem to be correlated with ageing. Despite the present study does not allow to draw definitive conclusions as the subjects analysed had a very narrow range of age, another study in an Italian population ranging from 10 to 79 years of age showed a correlation between increased peripheral IP-10 levels and ageing [5]. An association between ageing and the inflammatory activity has been demonstrated, although it’s not clear whether increased inflammatory activity causes age-associated pathology or reflect the sum of ongoing pathologic processes [6]. ApoE e4 was strongly associated with AD in our samples, but e4 carrier status by itself did not predict conversion to AD, in accordance with recent findings [7].