Dementia with Lewy Bodies: Molecular Pathology in the Frontal Cortex in Typical and Rapidly Progressive Forms

These results suggest energy metabolism impairment in frontal cortex in dementia with Lewy bodies and rapid DLB

Paula Garcia-Esparcia; Irene López-González; Oriol Grau-Rivera; María Francisca García-Garrido; Anusha Konetti; Franc Llorens; Saima Zafar; Margarita Carmona; José Antonio del Rio; Inga Zerr; Ellen Gelpi; Isidro Ferrer

2017

Scholarcy highlights

  • Dementia with Lewy bodies is the second most common neurodegenerative dementia in the elderly, clinically manifested by fluctuating cognition with pronounced variation in attention and alertness, recurrent visual hallucinations which are typically well formed and detailed, and spontaneous motor features of parkinsonism; repeated falls, syncope, transient loss of consciousness, systematized delusions, hallucinations in other modalities, and neuroleptic sensitivity are not uncommon
  • neurofibrillary tangle in frontal cortex occurred in two dementia with Lewy bodies and two rapid DLB cases
  • Changes are represented with the corresponding p-value and mRNA levels are expressed as mean fold change ± SD determined by real-time quantitative PCR and analyzed with the ΔΔCT method: *p < 0.05, **p < 0.01, and ***p < 0.001
  • Present biochemical studies have shown similar percentages of Aβ40 and Aβ42 in plaques in DLB and rpDLB abnormal solubility and aggregation of α-synuclein and increased β-amyloid bound to membranes in the frontal cortex in DLB and rpDLB
  • Molecular alterations in the cerebral cortex in DLB include deregulated expression of several mRNAs and proteins of mitochondrial subunits and reduced activity of complexes I, II, III, and IV of the mitochondrial respiratory chain; reduced expression of selected molecules involved in energy metabolism and increased expression of enzymes involved in purine metabolism; abnormal expression of certain nucleolar proteins, rRNA18S, genes encoding ribosomal proteins and initiation factors of the transcription at the ribosome; discrete inflammation; and marked deregulation of brain Olfactory receptor and taste receptor
  • No significant differences in gene expression of several cytokines and mediators of the inflammatory response are seen in DLB
  • Altered solubility and aggregation of α-synuclein, increased β-amyloid bound to membranes, and absence of soluble tau oligomers are common in DLB and DLB with rapid progression
  • Since high levels of soluble β-amyloid species are toxic for nerve cells and TNF-α

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