The expression of clusterin in the entorhinal cortex in Parkinson’s disease: a pilot
study
1,2
Karin D. van Dijk , Wilma D.J. van de Berg
1
1
2
Dept. of Anatomy and Neurosciences, section Functional Neuroanatomy, Dept. of Neurology,
Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Research question and background
Clusterin is a multifunctional chaperone protein that is expressed in a variety of tissues
including the brain and has repeatedly been linked to Alzheimer’s disease (AD)
pathogenesis. Recently, a specific clusterin encoding single-nucleotide polymorphism
was reported to be associated with Parkinson’s disease (PD) [1]. This association was
most pronounced in PD patients with dementia, suggesting that cortical Lewy Body
pathology or concomitant AD pathology in the PD patients might play a role. Previously,
we measured clusterin levels in cerebrospinal fluid of PD patients and controls and
found that clusterin levels in cerebrospinal fluid (CSF) correlated with CSF levels of the
AD-related markers total tau, phospho-tau and amyloid-β-42 [2]. The current pilot project
was aimed to get more insight into the role of clusterin in PD and its relation with the
protein tau in PD. Therefore, we studied clusterin expression, including clusterin
localization and its relation to tangle pathology in post-mortem Parkinson’s disease.
Methods and tissues used
Paraffin-embedded post-mortem tissue from the entorhinal region of four clinically and
pathologically confirmed PD patients, four non-demented controls and two clinically and
pathologically confirmed AD patients were obtained from the Netherlands Brain Bank
(NBB). Immunohistochemical stainings of clusterin and tau on ten micrometer thick
sections was performed. In PD patients and controls, clusterin expression and tangle
pathology were quantified by a semi-quantitative method based on immunopositive cell
counts.
Results and conclusion
We observed both intraneuronal (graunules and larger aggregates) and extraneuronal
(plaque-like structures) clusterin immunoreactivity in the entorhinal region of PD patients
and controls. Semiquantitative analysis indicated a trend towards a higher degree of
extracellular clusterin staining in the entorhinal cortex of PD patients compared to
controls that tended to negatively correlate with tangle pathology. These
neuropathological findings confirm a possible relationship between clusterin and tau
pathology in PD patients.
References
[1]
Gao J, Huang X, Park Y, Hollenbeck A, Chen H. An exploratory study on CLU,
CR1 and PICALM and Parkinson disease. PLoS one 2011; 6: e2411.
[2]
van Dijk KD, Jongbloed W, Heijst JA, Teunissen CE, Groenewegen HJ,
Berendse HW, van de Berg WDJ, Veerhuis R. Accepted for publication in
Parkinonism and Related Disorders 2013.