December 2010
Beyer K, Domingo-Sàbat M, Santos C, Tolosa E, Ferrer I, Ariza A
Lewy body diseases include dementia with Lewy bodies and Parkinson’s
disease. Whereas dementia with Lewy bodies and Parkinson’s
disease can be distinguished as separate clinical
entities, the pathological picture is very often identical. α-synuclein
aggregation is a key event in the pathogenesis of
Lewy body diseases and β-synuclein inhibits α-synuclein aggregation in vitro and in vivo.
Recently, β-synuclein has been shown to interact directly with
α-synuclein, regulating its functionality and preventing
its oligomerization.
In this study, we analysed the
expression of two β-synuclein transcript variants and the main
α-synuclein
transcript SNCA140, in frozen samples of
three areas from brains of patients with (i) pure diffuse Lewy body
pathology; (ii) pure Alzheimer’s
disease pathology; (iii) diffuse Lewy body
pathology and concomitant Alzheimer’s disease pathology and (iv)
controls.
Relative
messenger RNA expression was determined by
real-time polymerase chain reaction, expression changes were evaluated
by the ΔΔCt method and messenger RNA expression data
were confirmed at the protein level.
A drastic diminution of
β-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
Alzheimer’s disease pathology or the clinical phenotype of Parkinson’s
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
β-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.
