Lewy body diseases include dementia with Lewy bodies and Parkinsons disease. Whereas dementia with Lewy bodies and Parkinsons disease can be distinguished as separate clinical entities, the pathological picture is very often identical. -synuclein aggregation is a key event in the pathogenesis of Lewy body diseases and -synuclein inhibits -synuclein aggregation in vitro and in vivo. Recently, -synuclein has been shown to interact directly with -synuclein, regulating its functionality and preventing its oligomerization. In this study, we analysed the expression of two -synuclein transcript variants and the main -synuclein transcript SNCA140, in frozen samples of three areas from brains of patients with (i) pure diffuse Lewy body pathology; (ii) pure Alzheimers disease pathology; (iii) diffuse Lewy body pathology and concomitant Alzheimers disease pathology and (iv) controls. Relative messenger RNA expression was determined by real-time polymerase chain reaction, expression changes were evaluated by the Ct method and messenger RNA expression data were confirmed at the protein level. A drastic diminution of -synuclein expression was observed in cortical areas of all samples that presented neuropathological features corresponding to pure diffuse Lewy body pathology and the clinical phenotype of dementia with Lewy bodies, but not in those with neuropathological features corresponding to diffuse Lewy body pathology and concomitant Alzheimers disease pathology or the clinical phenotype of Parkinsons disease with dementia. The correlation of expression data with the clinical phenotype and neuropathological diagnosis of the patients suggested the existence of a specific molecular subtype of dementia with Lewy bodies, characterized by a strong decrease of -synuclein in the frontal and temporal cortices. Furthermore, our findings provide new insights into the pathogenesis of Lewy body diseases that may be important for the understanding of molecular mechanisms involved in these complex diseases.

EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000427 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000427 | SxmlIndent | more

{{Explor lien
   |wiki=    Wicri/Sante
   |area=    ParkinsonV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     ISTEX:6BBF9B326D67DFDB7F8C32E63533539F3BA561DB
   |texte=   The decrease of -synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies
}}