A comparison between rectal and colonic biopsies to detect Lewy pathology in Parkinson's disease

Pouclet, Hélène; Lebouvier, Thibaud; Coron, Emmanuel; Varannes, Stanislas Bruley des; Rouaud, Tiphaine; Roy, Monica; Neunlist, Michel; Derkinderen, Pascal

doi:10.1016/j.nbd.2011.08.014

Cited by 126 publications

(114 citation statements)

References 17 publications

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“…One study used an antibody that was not specific for phosphorylated a-synuclein 21 whereas the other used an antibody specific for phosphorylated a-synuclein. 32 This may have implications for the present study.…”

Section: Figurementioning

confidence: 83%

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α-Synuclein in cutaneous autonomic nerves

et al. 2013

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Objective: To develop a cutaneous biomarker for Parkinson disease (PD).Methods: Twenty patients with PD and 14 age-and sex-matched control subjects underwent examinations, autonomic testing, and skin biopsies at the distal leg, distal thigh, and proximal thigh. a-Synuclein deposition and the density of intraepidermal, sudomotor, and pilomotor nerve fibers were measured. a-Synuclein deposition was normalized to nerve fiber density (the a-synuclein ratio). Results were compared with examination scores and autonomic function testing.Results: Patients with PD had a distal sensory and autonomic neuropathy characterized by loss of intraepidermal and pilomotor fibers (p , 0.05 vs controls, all sites) and morphologic changes to sudomotor nerve fibers. Patients with PD had greater a-synuclein deposition and higher a-synuclein ratios compared with controls within pilomotor nerves and sudomotor nerves (p , 0.01, all sites) but not sensory nerves. Higher a-synuclein ratios correlated with Hoehn and Yahr scores (r 5 0.58-0.71, p , 0.01), with sympathetic adrenergic function (r 5 20.40 to 20.66, p , 0.01), and with parasympathetic function (r 5 20.66 to 20.77, p . 0.01). Conclusions:We conclude that a-synuclein deposition is increased in cutaneous sympathetic adrenergic and sympathetic cholinergic fibers but not sensory fibers of patients with PD. Higher a-synuclein deposition is associated with greater autonomic dysfunction and more advanced PD. These data suggest that measures of a-synuclein deposition in cutaneous autonomic nerves may be a useful biomarker in patients with PD. Accumulating evidence suggests that a-synuclein deposition occurs early in the course of PD and may antedate the appearance of the clinical features of the disease.2 This has provided the rationale for the use of a-synuclein as a biomarker in PD. 3Skin punch biopsy could provide a simple means to measure a-synuclein deposition in the peripheral nervous system; however, preliminary studies used techniques optimized for CNS tissue, relied on small tissue volumes, and did not systematically study autonomic substructures, and therefore detected a-synuclein in only a minority of subjects with PD. [4][5][6][7][8] We recently reported novel methods to study the cutaneous autonomic innervation in skin biopsies of patients with peripheral nerve disease.9,10 We hypothesized, based on the prominent autonomic manifestations of PD, that a-synuclein deposition would be elevated in cutaneous structures with autonomic innervation.The aims of the study were to determine 1) whether a-synuclein was present in cutaneous sensory and autonomic nerves, 2) the relationship between cutaneous a-synuclein deposition and *These authors contributed equally to this work.

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Section: Figurementioning

confidence: 83%

“…However, discordant results have been reported. 32 The discrepancy may be related to the specificity of the antibody used in the 2 studies. One study used an antibody that was not specific for phosphorylated a-synuclein 21 whereas the other used an antibody specific for phosphorylated a-synuclein.…”

Section: Figurementioning

confidence: 99%

α-Synuclein in cutaneous autonomic nerves

et al. 2013

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“…Moreover, the presence of Lewy pathology in colonic biopsies (Lebouvier et al 2008(Lebouvier et al , 2010Pouclet et al 2011;Shannon et al 2012) indicates that the intramural plexus in the lower gastrointestinal tract might be an additional source of a route for retrograde dissemination of synucleinopathy to the dmX. Currently, no definitively confirmed autopsy-based evidence exists for either phenomenon (Beach et al During stages 5 and 6 (dark/light pink), lesions develop chiefly in projection neurons of the deep layers of the neocortex, beginning in the high-order sensory association areas and prefrontal fields.…”

Section: Spread Of Pathological A-synuclein Lesions In Pdmentioning

confidence: 99%

Potential Pathways of Abnormal Tau and α-Synuclein Dissemination in Sporadic Alzheimer's and Parkinson's Diseases

Braak

Tredici

2016

Cold Spring Harb Perspect Biol

105

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Experimental data indicate that transneuronal propagation of abnormal protein aggregates in neurodegenerative proteinopathies, such as sporadic Alzheimer's disease (AD) and Parkinson's disease (PD), is capable of a self-propagating process that leads to a progression of neurodegeneration and accumulation of prion-like particles. The mechanisms by which misfolded tau and a-synuclein possibly spread from one involved nerve cell to the next in the neuronal chain to induce abnormal aggregation are still unknown. Based on findings from studies of human autopsy cases, we review potential pathways and mechanisms related to axonal and transneuronal dissemination of tau (sporadic AD) and a-synuclein (sporadic PD) aggregates between anatomically interconnected regions. S poradic Alzheimer's disease (AD) and Parkinson's disease (PD) are human neurodegenerative disorders that do not occur in other vertebrate species. Pathological hallmark lesions in AD and PD involve only a few types of nerve cells, mainly projection neurons. These lesions develop at predetermined predilection sites and progress according to predictable patterns (Braak and Del Tredici 2009, 2015). In AD, disease-related lesions remain confined to the central nervous system (CNS), whereas in PD they develop not only in the CNS but also in the enteric (ENS) and peripheral (PNS) nervous systems. Both diseases are caused by misfolding of specific proteins that are associated with aberrant aggregation. AD is primarily characterized by pathological forms of the intraneuronal protein tau (Goedert et al. 2006;Iqbal et al. 2009) and, thereafter gradually, by extracellular deposits of the b-amyloid protein (Ab) (Alafuzoff et al. 2009;Haass et al. 2012;Masters and Selkoe 2012). In mature nerve cells, the highest concentrations of the protein tau usually are found in the axon. Key lesions in sporadic PD consist of aggregated forms of a-synuclein, a protein located chiefly in axons and their presynaptic terminals (Eisenberg and Jucker 2012;Jucker and Walker 2013;Kaufman and Diamond 2013;Goedert et al. 2014). Notably, all brain regions and all types of nerve cells consecutively involved in AD or PD are anatomically interconnected over considerable distances, thereby indicating that physical contact among such interconnected nerve cells plays a key role in the pathogenesis of both illnesses (Pearson et al. 1985;Saper et al. 1987;Pearson and Powell 1989;Pearson 1996;Duyckaerts et al. 1997;Braak and Del Tredici 2011b). Ab is deposited extracellularly and thus is not known to transfer from one nerve cell to the next in the neuronal chain (Fiala 2007;Kaufman and Diamond 2013).Here, we focus on potential pathways and mechanisms related to the postulated transmission and transneuronal dissemination of tau and a-synuclein between involved neurons and as yet uninvolved neurons in anatomically connected regions (Brundin et al. 2008Clavaguera et al. 2009Clavaguera et al. , 2013aDesplats et al. 2009;Luk et al. 2009;Angot et al. 2010 Angot et al. , 2012Frost and Diamond 2010;Goedert...

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“…5 One clinical study and multiple autopsy studies suggest rectal biopsy would not be of value. 12,22,23,29,31,33 The skin has also been investigated as a biomarker for PD; however, multiple studies have found minimal LTS in the skin. 6,12 Other areas of biomarker development include assessing proteins in the CSF and saliva.…”

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confidence: 99%

Submandibular gland needle biopsy for the diagnosis of Parkinson disease

et al. 2014

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Objective: This study investigates salivary gland biopsies in living patients with Parkinson disease (PD). Methods:Patients with PD for $5 years underwent outpatient transcutaneous needle core biopsies (18-gauge or 16-gauge) of 1 submandibular gland. Minor salivary glands were removed via a small incision in the lower lip. Tissue was fixed in formalin and serial 6-mm paraffin sections were immunohistochemically stained for phosphorylated a-synuclein and reviewed for evidence of Lewy type a-synucleinopathy (LTS).Results: Fifteen patients with PD were biopsied: 9 female/6 male, mean age 68.7 years, mean PD duration 11.8 years. Twelve of the needle core biopsies had microscopically evident submandibular gland tissue to assess and 9/12 (75%) had LTS. Only 1/15 (6.7%) minor salivary gland biopsies were positive for LTS. Five patients had an adverse event; all were minor and transient. Conclusions:This study demonstrates the feasibility of performing needle core biopsies of the submandibular gland in living patients with PD to assess LTS. Although this was a small study, this tissue biopsy method may be important for tissue confirmation of PD in patients being considered for invasive procedures and in research studies of other PD biomarkers.

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A comparison between rectal and colonic biopsies to detect Lewy pathology in Parkinson's disease

Cited by 126 publications

References 17 publications

α-Synuclein in cutaneous autonomic nerves

α-Synuclein in cutaneous autonomic nerves

Potential Pathways of Abnormal Tau and α-Synuclein Dissemination in Sporadic Alzheimer's and Parkinson's Diseases

Submandibular gland needle biopsy for the diagnosis of Parkinson disease

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