Background and purpose: Expression of the mitochondrial fission proteins dynamin-related protein 1 (Drp1), S-nitrosylated Drp1 (SNO-Drp1), and Fis1 has been found to be altered in brain tissues and skin fibroblasts from patients with Alzheimers disease (AD). The aim of this study was to determine whether these proteins are also changed in peripheral blood lymphocytes (PBL) of AD patients and whether these changes are specific and sensitive enough for AD diagnosis. Methods: Western blot analysis and enzyme-linked immunosorbent assay (ELISA) were employed to quantify relative levels of Drp1, SNO-Drp1, and Fis1 in PBL obtained from 91 controls, 82 AD, 26 mild cognitive impairment (MCI), 12 Parkinsons disease (PD), and 36 vascular dementia (VaD) patients. Logistic regression and receiver operating characteristic (ROC) curve analysis were used to measure diagnostic accuracy of these proteins. Results: Compared with controls, SNO-Drp1 and Fis1 levels were remarkably increased in PBL of AD and MCI patients, and Drp1 was significantly decreased in AD, MCI, and PD. None of these proteins were changed in VaD patients. Disease severity or duration had no major effects on levels of these proteins in AD PBL. ROC curve analysis showed that the specificity and sensitivity were 81% and 73% for Drp1, 84% and 82% for SNO-Drp1, and 89% and 80% for Fis1 in identifying AD patients from control subjects. Conclusions: Altered mitochondrial fission proteins Drp1, SNO-Drp1, and Fis1 in PBL were relatively sensitive and specific in identifying AD patients and could be serving as a biomarker in the procedure of diagnosis.