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P4‐042: White matter damage in frontotemporal lobar degeneration spectrum
Author(s) -
Agosta Federica,
Scola Elisa,
Canu Elisa,
Marcone Alessandra,
Magnani Giuseppe,
Sarro Lidia,
Copetti Massimiliano,
Caso Francesca,
Cerami Chiara,
Comi Giancarlo,
Cappa Stefano,
Andrea Falini,
Filippi Massimo
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.2062
Subject(s) - frontotemporal lobar degeneration , frontotemporal dementia , semantic dementia , primary progressive aphasia , white matter , diffusion mri , atrophy , pathology , medicine , posterior cortical atrophy , voxel , voxel based morphometry , dementia , psychology , magnetic resonance imaging , radiology , disease
appear to be triggered by the progressive intracellular accumulation of specific yet unrelated toxic proteins that target select cell populations. Different mechanisms have been proposed to explain neurodegeneration for instance the p53, JNK and PI3K/Akt signaling pathways are reported to be affected by intracellular b-amyloid (Ab) peptide. The clinically important consequence of these various events is synaptic loss and multiple neurotransmitter deficits. Detrimental alterations in conformation of a native protein that makes it resistant to degradation are relevant to Alzheimer’s disease pathology. One of the key homeostatic responses in protein misfolding disorders is the induction of heat shock proteins, a conserved reaction to damaged intracellular proteins. Methods: Immunofluorescence and ultrastructural. Results: Immunofluorescence and ultrastructural studies confirmed Ab localization in the endoplasmic reticulum and in small vesicles andmultivesicular bodies. Approximately 50% of vesicular-associated immunogold labeling was found located on the membrane. No intracellular aggregates of Ab were observed by microscopy techniques, and no higher molecular weight species were detected byWestern blot.Conclusions: These data suggest that soluble Ab in intracellular compartments is toxic without fibril or aggregate formation. Biochemical analysis showed an upregulation of Hsp90/70 in response to intraneuronal Ab expression. Thus, we hypothesized that an imbalance between the neuronal Hsp capacity and the toxic accumulation of Ab may be responsible for the observed neuron death.