Prevalence of Submandibular Gland Synucleinopathy in Parkinson’s Disease, Dementia with Lewy Bodies and other Lewy Body Disorders

Beach, Thomas G.; Adler, Charles H.; Serrano, Geidy E.; Sue, Lucia I.; Walker, Douglas G.; Dugger, Brittany N.; Shill, Holly A.; Driver‐Dunckley, Erika; Caviness, John N.; Intorcia, Anthony; Filon, Jessica; Scott, Sarah; Garcia, Angelica; Hoffman, Brittany; Belden, Christine M.; Davis, Kathryn; Sabbagh, Marwan N.

doi:10.3233/jpd-150680

Cited by 57 publications

(50 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…75 However, this group of researchers has not encountered a single case in which pathological a-syn was present in a peripheral body region but not in the CNS. 66 In contrast, Japanese studies have reported a number of cases with isolated a-syn pathology in the myenteric plexus of the esophagus and small intestine, the paraspinal sympathetic ganglia, adrenal glands, and also some cases with pathology restricted to the ganglia and thoracic IML. 30, [76][77][78] It should be noted that 1 of these studies was published prior to the era of a-syn immunohistochemistry, and the findings should be interpreted with caution.…”

Section: Pathological A-syn In Peripheral Organsmentioning

confidence: 95%

“…In diagnosed PD patients, pathological a-syn aggregations have been detected in various peripheral tissues, including the nervous plexuses of the gastrointestinal tract, [59][60][61][62][63] , heart, 64 salivary glands, 63,65,66 and skin. 67,68 However, to assess whether pathological a-syn appears during the preclinical phase, studies of prodromal cases, archived tissues, and autopsy material from neurologically intact individuals with or without incidental Lewy body disease (ILBD) are necessary.…”

Section: Pathological A-syn In Peripheral Organsmentioning

confidence: 99%

See 1 more Smart Citation

How does parkinson's disease begin? Perspectives on neuroanatomical pathways, prions, and histology

Borghammer

2017

Movement Disorders

120

View full text Add to dashboard Cite

Parkinson's disease (PD) is a multisystem disorder with involvement of the peripheral nervous system. Misfolding and aggregation of α-synuclein is central to the pathogenesis of PD, and it has been postulated that the disease may originate in olfactory and gastrointestinal nerve terminals. The prion-like behavior of α-synuclein has been convincingly demonstrated in vitro and in animal models of PD. Lewy-type pathology have been detected in peripheral organs many years prior to PD diagnosis, and 2 independent studies have now suggested that truncal vagotomy may be protective against the disorder. Other lines of evidence are difficult to reconcile with a peripheral onset of PD, most importantly the relative scarcity of post mortem cases with isolated gastrointestinal α-synuclein pathology without concomitant CNS pathology. This Scientific Perspectives article revisits some important topics with implications for the dual-hit hypothesis. An account of the neuroanatomical pathways necessary for stereotypical α-synuclein spreading is presented. Parallels to the existing knowledge on true prion disorders, including Creutzfeld-Jakob disease, are examined. Finally, the vagotomy studies and the somewhat inconsistent findings in the growing literature on peripheral α-synuclein pathology are discussed. It is concluded that the dual-hit hypothesis remains a potential explanation for PD pathogenesis, but several issues need to be resolved before more firm conclusions can be drawn. © 2017 International Parkinson and Movement Disorder Society.

show abstract

Section: Pathological A-syn In Peripheral Organsmentioning

confidence: 95%

Section: Pathological A-syn In Peripheral Organsmentioning

confidence: 99%

How does parkinson's disease begin? Perspectives on neuroanatomical pathways, prions, and histology

Borghammer

2017

Movement Disorders

120

View full text Add to dashboard Cite

show abstract

“…Post-mortem submandibular gland biopsies are positive for Lewy-type a-syn in patients with PD but not in healthy subjects [71], and this finding has made salivary a-syn one of the most investigated salivary biomarkers in neurodegeneration. Yet, both increases and decreases in salivary total a-syn have been reported [72][73][74].…”

Section: Alpha-synucleinmentioning

confidence: 99%

Salivary Biomarkers for Alzheimer’s Disease and Related Disorders

et al. 2019

View full text Add to dashboard Cite

The search for accessible and cost-effective biomarkers to complement current cerebrospinal fluid (CSF) and imaging biomarkers in the accurate detection of Alzheimer disease (AD) and other common neurodegenerative disorders remains a challenging task. The advances in ultra-sensitive detection methods has highlighted blood biomarkers (e.g. amyloidb and neurofilament light) as a valuable and realistic tool in a diagnostic or screening process. Saliva, however, is also a rich source of potential biomarkers for disease detection and offers several practical advantages over biofluids that are currently examined for neurodegenerative disorders. However, while this may be true for the general population, challenges in collecting saliva from an elderly population should be seriously considered. In this review, we begin by discussing how saliva is produced and how age-related conditions can modify saliva production and composition. We then focus on the Enhanced digital features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.9792335.

show abstract

“…Lewy body pathology has been reported to occur in early stages of PD in the submandibular gland and gut (Beach et al . ; Uchihara and Giasson ; Uchihara et al . ).…”

Section: Biomarkers For α‐Synuclein Pathologymentioning

confidence: 99%

Fluid‐based proteomics targeted on pathophysiological processes and pathologies in neurodegenerative diseases

Brinkmalm

Portelius

Brinkmalm

et al. 2018

Journal of Neurochemistry

View full text Add to dashboard Cite

Neurodegenerative dementias constitute a broad group of diseases in which abnormally folded proteins accumulate in specific brain regions and result in tissue reactions that eventually cause neuronal dysfunction and degeneration. Depending on where in the brain this happens, symptoms appear which may be used to classify the disorders on clinical grounds. However, brain changes in neurodegenerative dementias start to accumulate many years prior to symptom onset and there is a poor correlation between the clinical picture and what pathology that is the most likely to cause it. Thus, novel drug candidates having disease-modifying effects that is targeting the underlying pathology and changes the course of the disease needs to be defined using objective biomarker-based measures since the clinical symptoms are often non-specific and overlap between different disorders. Furthermore, the treatment should ideally be initiated as soon as symptoms are evident or when biomarkers confirm an underlying pathology (pre-clinical phase of the disease) to reduce irreversible damage to, for example, neurons, synapses and axons. Clinical trials in the pre-clinical phase bring a greater importance to biomarkers since by definition the clinical effects are difficult or slow to discern in a population that is not yet clinically affected. Here, we discuss neuropathological changes that may underlie neurodegenerative dementias, including how they can be detected and quantified using currently available biofluid-based biomarkers and how more of them could be identified using targeted proteomics approaches.

show abstract

Prevalence of Submandibular Gland Synucleinopathy in Parkinson’s Disease, Dementia with Lewy Bodies and other Lewy Body Disorders

Cited by 57 publications

References 86 publications

How does parkinson's disease begin? Perspectives on neuroanatomical pathways, prions, and histology

How does parkinson's disease begin? Perspectives on neuroanatomical pathways, prions, and histology

Salivary Biomarkers for Alzheimer’s Disease and Related Disorders

Fluid‐based proteomics targeted on pathophysiological processes and pathologies in neurodegenerative diseases

Contact Info

Product

Resources

About