DOI: 10.1002/alz.078278 ISSN: 1552-5260

Alzheimer’s Disease as a potential diabetes type III: Pilot Study of comorbidities related to AD

Andrea González, Calfio Camila, Ricardo Benjamin Maccioni, Gonzalo Farías, Patricio Fuentes
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology

Abstract

Background

Alzheimer’s disease (AD) is the most prevalent cause of dementia in the elderly population. It is a multifactorial disease in which metabolic dysregulation and glucose metabolism impairment plays a major role in the etiopathogenesis. In this research, we evaluate the comorbidities in a clinical trial for the novel biomarker Alz‐tau®, based on platelet tau, in cognitive healthy controls, mild‐cognitive impairment (MCI) and AD patients, in particular TII diabetes. Alterations in this biomarker appear to indicate high risk of developing AD, as demonstrated in previous clinical trials.

Methods

From a cohort of 111 subjects, neuropsychology tests were performed to assign the respective group (control, MCI or AD). In addition, a health questionnaire to evaluate comorbidities. For the Alz‐tau® biomarker, platelets were obtained from plasma by centrifugation, lysed to obtain platelet protein extracts (containing tau) and further processed for a western blot analysis. The immuno‐ detection was performed with our novel monoclonal antibody tau51, which detects two variants of tau protein: a high molecular weight variant (HMW) and a low molecular weight variant (LMW). The results obtained were subjected to a densitometric analysis with ImageJ and the algorithm HWM/LMW was obtained.

Result

From 111 patients, 17 presented diabetes type 2 as a comorbidity (15,3%). Out of them, 11 were cognitive healthy subjects (64.7%), 4 EA patients (23.5%) and 2 MCI (11.8%). Out of the control patients, 6 have the Alz‐tau® biomarker altered (54.5%), which was similar to what was observed in the EA patients (2 patients, 50%) and the MCI (1 patient, 50%). Of the 17 patients with diabetes, 53% presented an altered Alz‐tau® biomarker (cut‐off 1.2 algorithm), which is considered a risk factor for AD. It should be considered that the area under the curve (AUC) of this novel biomarker Alz‐tau® is 0.69, appropriate for a novel technique.

Conclusion

Here, we discovered that this early detection biomarker is correlated with the high‐risk factor of having AD in the future, since non‐symptomatic subjects exhibited an altered biomarker. Moreover, more than 50% of the TII diabetic positive cognitive healthy controls, exhibit an altered biomarker, sustaining our hypothesis of the correlation between glucose‐metabolism impairment, AD and oligomeric tau.

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