Parkinson’s disease is a debilitating neurodegenerative movement disorder, characterized by the progressive and selective loss of dopaminergic neurons located in the substantia nigra, leading to clinical motor symptoms. The factors involved in PD are rather multifaceted. There are many cellular pathways contributing to its neuro-pathogenesis, which include abnormal protein aggregation, impaired ubiquitin proteasome system, autophagy, and neuroinflammation. However, despite years of investigation, still little is known about early events in the molecular pathogenesis. MicroRNAs are small non-coding RNAs that can regulate post-transcriptional expression of mRNAs. Since they somewhat modulate many mRNA targets simultaneously, many cellular pathways may be affected by one individual miRNA. Moreover, miRNAs can stably circulate in cerebrospinal fluid and blood, and their expression pattern can reflect the molecular pathophysiology, thus making them promising biomarkers in PD diagnosis and prognosis. In this review, we will review the recent progress on miRNA’s mechanism in PD pathogenesis and discuss the possibilities of miRNAs as PD molecular biomarkers.

Gantenerumab, a human anti-Aβ antibody designed to bind aggregated Aβ and promote plaque removal, was studied in SCarlet RoAD (NCT01224106; WN25203)—a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-year trial in prodromal AD. Dosing was terminated in December 2014 following a pre-planned futility analysis; patients continue to be followed. CSF biomarker data and amyloid PET sub-study results are presented (patients completing 2-year treatment). Eligible patients were 50–85 years old, had MMSE scores ≥24, CDR-Global scores of 0.5 (memory box scores of 0.5 or 1.0) and evidence of amyloid pathology (CSF Aβ42 <600 ng/mL, Innotest®), with cognitive and functional performance largely preserved to exclude a diagnosis of dementia. Patients were randomized to monthly subcutaneous injections of placebo, or 105 mg or 225 mg gantenerumab, based on APOEe4 allele status (no APOEe4 homozygotes received 225 mg). CSF biomarkers were analyzed using Elecsys® β-Amyloid(1–42), tTau and pTau(181P) immunoassays (Roche Diagnostics; these products are in development and not available in the USA). 114 patients were enrolled in a PET sub-study (AmyvidTM). Standardized uptake value (SUVr), normalized to different reference regions, was assessed. Clinical results are presented separately. Amyloid-PET observed mean % change (± SD) from baseline in cortical composite SUVr (using mean cerebellar grey as reference region) at Week 100: placebo (n=20) -1.11 ± 8.02; 105 mg gantenerumab (n=11) +0.19 ± 12.70; 225 mg gantenerumab (n=18) -5.37 ± 7.92. No changes in CSF Aβ42 levels were found. CSF p-Tau mean % change (± SD) from baseline at Week 104: placebo (n=63) +2.62 ± 21.89; 105 mg gantenerumab (n=62) -4.85 ± 12.42; 225 mg gantenerumab (n=58) -7.52 ± 9.85. CSF t-Tau: mean % change (± SD) from baseline at Week 104: placebo (n=62) +3.11 ± 21.12; 105 mg gantenerumab (n=60) -1.45 ± 13.55; 225 mg gantenerumab (n=57) -2.94 ± 10.37. At the doses tested, gantenerumab treatment was associated with dose-dependent reductions in brain Aβ SUVr and CSF p-Tau and t-Tau, compared with placebo. As expected, CSF Aβ42 levels were unaltered. These findings are consistent with brain amyloid clearance and an effect on downstream markers of neurodegeneration.