Skin biopSYN or how to predict Parkinson's disease

Don't get confused, there is no typo nor editing mistake in the title of this Editorial as ‘Skin biopSYN’ stands for ‘detection of alpha-synuclein in skin biopsies’. Skin has become a hot topic in Parkinson's disease (PD) and there has been an exponential growth research over recent years. Following the observation that Lewy bodies and neurites from the brain of sporadic PD patients were highly immunoreactive for alpha-synuclein, alpha and phospho-alpha-synuclein immunohistochemical staining quickly became the method of choice for the neuropathological diagnosis of PD [1,2]. Using this approach, several neuropathology laboratories demonstrated that phospho-alpha-synuclein histopathology (PASH) is not limited to the brain but also widespread throughout the peripheral autonomic networks [3], including the autonomic innervation of the skin [4]. This is of particular interest because the development of biomarkers for PD has been hampered by the fact that the core pathology lies in the brainstem, deeply buried and hidden from direct study in living patients. In this context, the accessibility of the skin with routine punch biopsies makes it a perfect candidate for the development of original histopathological markers that will directly evaluate the pathological process in PD [5]. This logically led several groups to study if immunohistochemical investigation for PASH in the biopsied skin may be a useful tool for the premortem diagnosis of PD. In the first paper on the topic, published in 2010, only 2 out of 20 parkinsonian patients were PASH + when skin punch biopsies of the chest were analyzed [6] (Fig. 1). It was not until 2014 that two independent groups convincingly showed that skin biopsies (performed at multiple sites and with optimized staining protocols) allowed to detect PASH and to discriminate between PD and controls with an acceptable sensitivity and an excellent specificity [7,8] (Fig. 1). The saga of skin biopsies as a potential histopathological marker for PD was launched and since then more than 30 studies on this subject have been published (reviewed in Ref. [9]).