A critical evaluation of current staging of alpha-synuclein pathology in Lewy body disorders

Biochimica Et Biophysica Acta
Kurt A Jellinger

Abstract

The two most frequent synucleinopathies, Parkinson disease (PD) or brainstem predominant type of Lewy body disease, and dementia with Lewy bodies (DLB), are neurodegenerative multisystem disorders with widespread occurrence of alpha-synuclein containing deposits in the central, peripheral, and autonomic systems. For both Lewy body-related disorders staging/classification systems based on semiquantitative assessment of the distribution and progression pattern of alpha-synuclein pathology are used that are considered to be linked to clinical dysfunctions. In PD a six-stage system is suggested to indicate a predictable sequence of lesions with ascending progression from medullary and olfactory nuclei to the cortex, the first two presymptomatic stages related to incidental Lewy body disease, stages 3 and 4 presenting with motor symptoms and the last two (cortical) stages frequently associated with cognitive impairment. DLB, according to consensus pathologic guidelines, by semiquantitative scoring of alpha-synuclein pathology (Lewy body density and distribution) in specific brain regions, is distinguished into three phenotypes (brainstem, transitory/limbic and diffuse cortical), also considering concomitant Alzheimer-related patholo...Continue Reading

References

Jul 1, 1995·Journal of Geriatric Psychiatry and Neurology·B J Beck
Jan 1, 1994·Acta Neuropathologica·D W DicksonJ Q Trojanowski
Jan 1, 1996·Journal of Neural Transmission·H BraakJ Bohl
Apr 28, 1999·Journal of Neuropathology and Experimental Neurology·D G DavisW R Markesbery
Jun 11, 1999·The Journal of Comparative Neurology·S Y MaE J Mufson
Aug 18, 1999·Journal of the Neurological Sciences·K WakabayashiH Takahashi
Nov 17, 1999·Neuropathology and Applied Neurobiology·S Y MaJ O Rinne
Sep 5, 2001·Neuropathology and Applied Neurobiology·L ParkkinenI Alafuzoff
Sep 18, 2001·Archives of Neurology·J L PriceJ C Morris
Mar 19, 2002·Journal of the Neurological Sciences·Wami MaruiKenji Kosaka
Aug 15, 2002·Neuropathology and Applied Neurobiology·C R CabelloB Pakkenberg
Oct 23, 2002·Brain : a Journal of Neurology·Antony J HardingGlenda M Halliday
Apr 26, 2003·Science·Benoit I GiassonVirginia M-Y Lee
Jun 5, 2003·Acta Neuropathologica·Kurt A JellingerGregor K Wenning
Jun 18, 2003·Journal of Neurology, Neurosurgery, and Psychiatry·C ColosimoA J Lees
Nov 1, 1960·Journal of Neurology, Neurosurgery, and Psychiatry·W A den HARTOG JAGER, J BETHLEM
Dec 17, 2003·Dementia and Geriatric Cognitive Disorders·John E Duda
Feb 10, 2004·Journal of Neural Transmission·H PrzuntekP Riederer
Aug 18, 2004·Journal of Geriatric Psychiatry and Neurology·Dag AarslandGlenda Halliday
Sep 1, 2004·Cell and Tissue Research·Heiko BraakKelly Del Tredici
Oct 14, 2004·Journal of Neural Transmission·K A Jellinger
Jul 1, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Miguel Angel Sánchez-GonzálezCarmen Cavada
Aug 11, 2005·Movement Disorders : Official Journal of the Movement Disorder Society·George K Tofaris, Maria Grazia Spillantini
Oct 1, 2005·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Ryoko YamamotoHeii Arai
Oct 21, 2005·Neurology·I G McKeithUNKNOWN Consortium on DLB
Dec 31, 2005·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Laura ParkkinenIrina Alafuzoff
Jan 27, 2006·Annals of Neurology·Benoit I GiassonVivianna M Van Deerlin

❮ Previous
Next ❯

Citations

Oct 13, 2009·Acta Neuropathologica·Michail E Kalaitzakis, Ronald K B Pearce
Nov 20, 2009·Acta Neuropathologica·Kurt A Jellinger
May 13, 2011·Acta Neuropathologica·Lisa FellnerNadia Stefanova
Jul 2, 2011·Acta Neuropathologica·Glenda M HallidayDennis W Dickson
Sep 4, 2009·Journal of Neurology·Kurt A Jellinger
Oct 2, 2009·Journal of Neurology·Peter T NelsonWilliam R Markesbery
Jun 22, 2010·Journal of Neurology·Peter T NelsonWilliam R Markesbery
Sep 24, 2010·Journal of Neural Transmission·Isidre FerrerMargarita Carmona
Sep 6, 2011·Journal of Neural Transmission·Hana Přikrylová VranováPetr Kaňovský
Nov 23, 2013·Parkinsonism & Related Disorders·Kelvin C Luk, Virginia M-Y Lee
Mar 11, 2009·Antioxidants & Redox Signaling·Saurabh Sen, Andrew B West
Aug 18, 2010·Antioxidants & Redox Signaling·Dalton James SurmeierJoshua A Goldberg
Jul 2, 2011·American Journal of Epidemiology·Xiang GaoAlberto Ascherio
Nov 30, 2011·TheScientificWorldJournal·Kurt A Jellinger
Oct 12, 2010·Science Translational Medicine·Bin ZhengUNKNOWN Global PD Gene Expression (GPEX) Consortium
Dec 19, 2012·Alzheimer's Research & Therapy·Amanda N Sacino, Benoit I Giasson
Aug 7, 2012·Disease Models & Mechanisms·Lilia ZurkovskyEugenia V Gurevich
Jun 5, 2013·Reviews in the Neurosciences·Nandakumar S NarayananErgun Y Uc
May 14, 2014·Annual Review of Neuroscience·Nele A HaeltermanHugo J Bellen
Nov 3, 2010·Annual Review of Pathology·Joshua M ShulmanMel B Feany
Jun 2, 2012·Expert Review of Neurotherapeutics·Glenda HallidayClaire Shepherd
Jan 30, 2014·Expert Review of Neurotherapeutics·Kurt A Jellinger
Sep 22, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·Elvira Valera, Eliezer Masliah
Feb 10, 2012·La Revue de médecine interne·S PaillussonP Derkinderen
Oct 26, 2011·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Zuzana Walker, Jeffrey L Cummings
Jun 28, 2012·Neurobiology of Disease·I FerrerA Martínez
Oct 18, 2011·Journal of the Neurological Sciences·Maria G Cersosimo, Eduardo E Benarroch
Jul 15, 2011·Parkinsonism & Related Disorders·Douglas E Hobson
Mar 15, 2015·Neurobiology of Disease·Dominik BrückLisa Fellner
Dec 20, 2011·Journal of Cellular and Molecular Medicine·Kurt A Jellinger
Oct 6, 2010·Movement Disorders : Official Journal of the Movement Disorder Society·Anne Marthe MeppelinkTeus van Laar
Jul 14, 2012·Movement Disorders : Official Journal of the Movement Disorder Society·David Sulzer, D James Surmeier
Nov 15, 2011·Movement Disorders : Official Journal of the Movement Disorder Society·Kurt A Jellinger
Sep 8, 2010·Movement Disorders : Official Journal of the Movement Disorder Society·Ann E KingsburyAndrew J Lees
Apr 17, 2013·Movement Disorders : Official Journal of the Movement Disorder Society·David Sulzer, D James Surmeier
Jan 5, 2011·CNS Neuroscience & Therapeutics·John N CavinessDouglas G Walker

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

Amygdala: Sensory Processes

Amygdalae, nuclei clusters located in the temporal lobe of the brain, play a role in memory, emotional responses, and decision-making. Here is the latest research on sensory processes in the amygdala.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Basal Forebrain- Circuits

Basal forebrain is a region in the brain important for production of acetylcholine and is the major cholinergic output of the CNS. Discover the latest research on circuits in the basal forebrain here.

Alpha-Synuclein Aggregation

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.

Atypical Parkinsonism (MDS)

Atypical Parkinsonism presents with the same signs and symptoms of Parkinson's disease, but do not respond to typical Parkionson's disease treatment with levodopa. Atypical Parkinsonism is thought to be associated with abnormal protein buildup within brain cells. Here is the latest on Atypical Parkinsonism.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.