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Neurodegeneration: General Aspects

  • Serge Weis
  • Michael Sonnberger
  • Andreas Dunzinger
  • Eva Voglmayr
  • Martin Aichholzer
  • Raimund Kleiser
  • Peter Strasser
Chapter
  • 382 Downloads

Abstract

Neurodegenerative disorders are complex, and heterogeneity is the rule, rather than the exception, even within a single disease entity. Neurodegenerative diseases can present clinically with predominantly cognitive symptoms (i.e., Alzheimer disease, fronto-temporal dementia, Lewy body dementia) or predominantly motor symptoms (i.e., Parkinson’s disease, Huntington disease, spinocerebellar ataxia).

Histologic changes include formation of abnormal structures in an extracellular location (amyloid deposits), in intracellular locations (intraneuronal: neurofibrillary tangle (NFT)), intracytoplasmic (Pick body, Lewy body), oligodendroglial (Papp-Lantos body), and other inclusions. Furthermore, loss of neurons, loss of synapses, glial changes, and vascular changes occur.

The molecular classification of neurodegenerative diseases differentiates between disorders with amyloid pathology, tauopathies, α-synucleinopathies, trinucleotide repeat disorders. Other genes involved include FUS, TDP-43, C9orf72, microtubule-associated proteins tau (MAPT), ubiquilin, ubiquilin 2, optineurin, and progranulin. Molecular pathways involve deposition of ß-sheet-rich proteins, protein-processing systems, unfolded protein response, ubiquitin-proteasome system, autophagy-lysosome pathway, modifications of disease-related proteins, maturation of protein deposits, neuronal loss due to different pathogenic pathways, metabolic changes, ion homeostasis, and neuro-inflammatory mechanisms.

The amyloid cascade hypothesis is discussed. Biomarker-based diagnostic algorithms for dementia syndromes are presented. A brief sketch of the differential diagnoses is presented including Pick disease, primary progressive aphasia (PPA), motor neuron disease with dementia, dementia lacking distinctive histopathology (DLDH), progressive subcortical gliosis (PSG), Parkinson’s disease with dementia, chromosome 17-associated dementia (Desinhibition-Dementia-Parkinsonism-Amyotrophy Complex), familial presenile dementia with tangles (FPDT), meso-limbo-cortical dementia Down syndrome (Trisomy 21), diffuse neurofibrillary tangles with calcifications (DNTC), thalamic degeneration, (non)-hereditary bilateral striatal necrosis, neuroacanthocytosis, pallidal degenerations, dentato-rubro-pallido-luysii degeneration, substantia reticularis degeneration, argyrophilic grain disease (AGD), adult polyglucosan body disease (APBD), normal pressure hydrocephalus (NPH), mitochondrial encephalomyopathies (Kearns-Sayre syndrome (KKS), myoclonic epilepsy with ragged-red fibers (MERF), mitochondrial encephalopathy, lactate, acidosis, and stroke-like episodes (MELAS), mitochondrial neurogastrointestinal encephalopathy (MNGIE)), Hallervorden-Spatz Disease, leukodystrophies, Wilson disease or hepato-lenticular degeneration, and dementia pugilistica.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Serge Weis
    • 1
  • Michael Sonnberger
    • 2
  • Andreas Dunzinger
    • 3
  • Eva Voglmayr
    • 2
  • Martin Aichholzer
    • 4
  • Raimund Kleiser
    • 2
  • Peter Strasser
    • 5
  1. 1.Division of Neuropathology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  2. 2.Department of Neuroradiology, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  3. 3.Department of Neuro-Nuclear Medicine, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  4. 4.Department of Neurosurgery, Neuromed CampusKepler University Hospital, Johannes Kepler UniversityLinzAustria
  5. 5.PMU University Institute for Medical & Chemical Laboratory DiagnosticsSalzburgAustria

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