Multiple organ involvement by alpha‐synuclein pathology in Lewy body disorders

Gelpí, Ellen; Navarro‐Otano, Judith; Tolosa, Eduardo; Gaig, Carles; Compta, Yaroslau; Rey, M.; Martı́, Marı́a José; Hernández, Isabel; Valldeoriola, Francesc; Rizzoli, René; Ribalta, Teresa

doi:10.1002/mds.25776

Cited by 321 publications

(261 citation statements)

References 34 publications

Supporting

Mentioning

247

Contrasting

Unclassified

Order By: Relevance

“…Alpha-synuclein aggregates are commonly found in the peripheral autonomic nervous system in both non-demented PD and LBD patients [51], which may explain why orthostatic hypotension was more commonly seen in our PD and LBD subjects than in the AD subjects. Orthostatic hypotension likely contributes to increased falls.…”

Section: Differentiation Of Pd and Ad From Lbd Subjects Based On Automentioning

confidence: 83%

Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer’s and Parkinson’s Diseases

Scharre

Chang

Nagaraja

et al. 2016

JAD

View full text Add to dashboard Cite

Abstract. Limited data compares clinical profiles of Lewy Body Dementia (LBD) with Alzheimer's disease (AD) andParkinson's disease (PD). Twenty-one mildly demented ambulatory LBD subjects were individually matched by MMSE score with 21 AD subjects and by UPDRS motor score with 21 PD subjects. Matched by age, gender, education, and race, pairs were compared using cognitive, functional, behavioral, and motor measures. LBD group performed worse than PD on axial motor, gait, and balance measures. AD had more amnesia and orientation impairments, but less executive and visuospatial deficits than LBD subjects. LBD group had more sleepiness, cognitive/behavioral fluctuations, hallucinations, and sleep apnea than AD or PD. Axial motor, gait, and balance disturbances correlated with executive, visuospatial, and global cognition deficits. LBD is differentiated from AD and PD by retrieval memory, visuospatial, and executive deficits; axial motor, gait and balance impairments; sleepiness, cognitive/behavioral fluctuations, hallucinations, and sleep apnea.

show abstract

Section: Differentiation Of Pd and Ad From Lbd Subjects Based On Automentioning

confidence: 83%

Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer’s and Parkinson’s Diseases

Scharre

Chang

Nagaraja

et al. 2016

JAD

View full text Add to dashboard Cite

show abstract

“…In addition, the majority of the cases with positivity in the optic nerve also showed positivity in the occipital cortex, suggesting spreading of the protein deposits in the course of disease. Pathologic deposits of ␣-synuclein are also known in the peripheral, including several cranial nerves [18], and autonomous nervous system as well as in other organs in Lewy body disorders [44]. It must be noted, however, that apart from the retina, the LGN receives input from regions, which are affected in Lewy body disorders (i.e.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Tau and α-Synuclein Pathology in the Visual System

Rahimi

Milenković

Kovács

2015

Journal of Parkinson’s Disease

View full text Add to dashboard Cite

Abstract.Background: Spreading of misfolded proteins has been suggested for neurodegenerative diseases. The hierarchical distribution of protein deposits in Alzheimer's (AD) and Parkinson's disease (PD) supports this concept. Objectives: To evaluate ␣-synuclein and tau-deposition in the optic pathway as an excellent anatomical model, which follows a strict trajectory including a cortico-geniculate feedback connection. Methods: We immunostained the optic nerve, lateral geniculate nucleus (LGN), and occipital cortex for AT8 (phosphorylated tau), ␣-synuclein, and disease-associated prion protein (PrP) in 47 cases with tau pathology (AD type, argyrophilic grain disease, or progressive supranuclear palsy), 16 PD, and 5 Creutzfeldt-Jakob disease (CJD) cases, respectively. Results: We detected immunoreactivity for all proteins along the optic pathway. The optic nerve showed immunopositivity only in cases with tau (6/8, 75%) or ␣-synuclein (5/7, 71%) pathology. The LGN was involved also frequently (tau: 22/47, 46.8%; ␣-synuclein: 15/16, 93.7%; PrP 5/5, 100%). The occipital cortex was variably affected by tau or ␣-synuclein pathology, but always showed PrP immunoreactivity in the CJD cases. Tau pathology in the LGN correlated with tau immunoreactivity in the occipital cortex and Braak stages of neurofibrillary degeneration. In tauopathies, which do not involve the occipital cortex, like argyrophilic grain disease or progressive supranuclear palsy, tau pathology was more frequently astrocytic in the LGN. Conclusions: Our results have implications 1) for the understanding of disease spreading along neural pathways and 2) for the diagnostic evaluation of the visual system in neurodegenerative proteinopathies as a potential biomarker to evaluate disease progression or subgrouping of cases.

show abstract

“…Pathological α-synuclein proteins called Lewy bodies have long been known to aggregatein the enteric nervous system (ENS) of patients diagnosed with PD and NCDLB [1][2][3][4][5][6][7][8][9][10][11][12][13]. Specifically, in PD and NCDLB, Lewy bodies appear in the myenteric plexus (MP) and the colonic submucosal plexus (CSMP) [8,[14][15][16][17][18][19][20].…”

Section: Cholinergic Lewy Pathology In the Ensmentioning

confidence: 99%

Mechanisms of α‐Synuclein Pathology and Treatment in the Enteric Nervous System

Lepkowsky¹

2017

IJGS

View full text Add to dashboard Cite

Abstractα-synuclein (Lewy Body) pathology is commonly found in the enteric nervous system (ENS) of patients diagnosed with Neurocognitive Disorder with Lewy Bodies (NCDLB) and Parkinson's Disease (PD). Lewy pathology in the ENS can produce symptoms of bowel immotility, including constipation, obstipation, and bowel impaction. These symptoms significantly reduce the quality of life for the patient, producing hardship for the patient and care providers. In Lewy body patients, medical intervention using acetylcholinesterase inhibitors (AChEIs) can significantly reduce or alleviate bowel immotility. The specific mechanism through which the cholinergic agonist Donepezil mitigates Lewy Body bowel immotility is explained. Practice, 1143 Deer Trail Lane, Solvang, California 93463, USA, Tel: 805-688-1229 Fax: 805-686-9382; E-mail: clepkowsky@gmail.com of α-synuclein aggregates in the MP predates cognitive and motor functional manifestations of Lewy body diseases so consistently that it has been nominated as a potential biomarker for Lewy pathology [10,17,30]. Symptomatic Manifestations of Cholinergic Lewy Pathology in the ENSLewy body cholinergic impairment in the ENS manifests symptomatically as gastric immotility and constipation [13,[31][32][33][34][35][36][37][38][39][40][41]. Increased colonic transit time and impaired gastric emptying are frequently found in PD patients [35,42]. The prevalence of constipation in PD is at least three times that of the general population, leading some researchersto suggest that constipation might be a universal feature of PD [47,48]. Bowel immotility can occur 20 years before diagnosis of PD or NCDLB, suggesting that it might be a prodromal symptom for both disorders [5,19,36,44,[49][50][51][52].As α-synuclein pathology advances in the ENS, symptoms of gastric immotility advance from constipation to obstipation and impaction. Escalating gastric immotility in PD and NCDLB can interfere with mobility, sleep, cognition, and mood, increasing the cost of care, and potentially debilitating and/or dramatically reducing the quality of life for patients. [4,34,36,[53][54][55][56] Potential Exacerbation of ENS Symptoms by AntiParkinson MedicationLPD and NCDLB patients with significant Parkinsonian motoric/gait features are often prescribed L-dopa agents like Carbidopa-Levodopa (known also by the brand names Sinemet and Stalevo) in order to preserve gait, balance, and other basic motor functions [40,57,58]. Carbidopa-Levodopa's potential side effects include constipation [59]. which can complicate or exacerbate gastric immotility due to ENS Lewy pathology. Medications frequently used for the treatment of resting tremor in PD and NCDLB includeTrihexyphenidyl (marketed as Artane or Trihex) and Benztropinemesylate (marketed as Cogentin), identified as definite anticholinergics that can also exacerbate gastric immotility through suppression of the cholinergic neurotransmitter pathways innervating the ENS [58,[60][61][62].

show abstract

Multiple organ involvement by alpha‐synuclein pathology in Lewy body disorders

Cited by 321 publications

References 34 publications

Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer’s and Parkinson’s Diseases

Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer’s and Parkinson’s Diseases

Patterns of Tau and α-Synuclein Pathology in the Visual System

Mechanisms of α‐Synuclein Pathology and Treatment in the Enteric Nervous System

Contact Info

Product

Resources

About