6-miRNA panel predicts amyloid status in cognitively normal older adults.

Joanna M. Williams^a*, Diane Guévremont^a, Chris Frampton^b, Margaret M. Ryan^a Chris J. Fowler^c,d, Colin L. Masters^d,e, Ralph N. Martins^d,f, Leslie M. Shaw^g, Alzheimer’s Disease Neuroimaging Initiative (ADNI)^h, Wickliffe C. Abrahamⁱ, Warren P. Tate^j, Nicholas J. Cutfield^k.

^a  Department of Anatomy, University of Otago, P.O. Box 56, Dunedin, 9054, New Zealand.

^b Department of Medicine, University of Otago, PO Box 4345, Christchurch, 8140, New Zealand

^c The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia. MD.

^d Australian Imaging, Biomarkers and Lifestyle (AIBL) Research GroupDepartment of Biomedical Sciences, Macquarie University, North Ryde 2113, New South Wales, 2109, Australia

^e University of Western Australia, Perth, Australia

^f Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia

^g University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia, PA 19104, USA

^h Alzheimer’s Disease Neuroimaging Initiative (ADNI)

ⁱ Department of Psychology, University of Otago, P.O. Box 56, 9016, Dunedin, New Zealand.

^j Department of Pathology and Molecular Medicine, University of Otago, P.O. Box 56, 9016, Dunedin, New Zealand.

^k Department of Medicine, University of Otago, P.O. Box 56, Dunedin, 9054, New Zealand.

 

*Corresponding author joanna.williams@otago.ac.nz

BACKGROUND: miRNA control neuronal functions dysregulated in Alzheimer’s disease (AD) and are highly stable in blood plasma. Previously, we have shown that plasma miRNA levels vary with the progression of  AD (Guévremont et al., 2022).

AIM: To identify miRNA capable of distinguishing cognitively normal older adults based on amyloid status.

STUDY SUMMARY:

Plasma neurodegeneration-related microRNA levels were assessed using TaqMan arrays in cognitively normal older adults who were Aβ+ or Aβ-.

In the AIBL discovery cohort, stepwise logistic regression identified a 6-miRNA panel that accurately differentiated cognitively normal, Aβ+ and Aβ- individuals (AUC = 0.990). The model was validated in ADNI (AUC=0.981) and KARVIAH (AUC=0.988) and distinguished amyloid converters (AUC 0.928) in a longitudinal AIBL cohort. Using a two-threshold approach, only 9% of samples fell within the intermediate classification zone (95% sensitivity and specificity).

CONCLUSION:

The 6-miRNA panel is a promising standalone biomarker of amyloid status which could enhance molecular diagnosis of Alzheimer’s disease.

 

Guévremont D, Tsui H, Knight R, Fowler CJ, Masters CL, Martins RN, et al. Plasma microRNA vary in association with the progression of Alzheimer's disease. Alzheimer's & dementia (Amsterdam, Netherlands). 2022;14(1):e12251