Title :

Clusterin/apolipoprotein j immunoreactivity is associated with white matter damage in cerebral small vessel diseases

Author(s) :

Craggs, Lucinda [Auteur]
Taylor, Julie [Auteur]
Slade, Janet Y. [Auteur]
Chen, Aiqing [Auteur]
Hagel, Christian [Auteur]
Kuhlenbaumer, Gregor [Auteur]
Borjesson-Hanson, Anne [Auteur]
Viitanen, Matti [Auteur]
Kalimo, Hannu [Auteur]
Deramecourt, Vincent [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172

Oakley, Arthur E. [Auteur]
Kalaria, Rajesh N. [Auteur]

Journal title :

Neuropathology and applied neurobiology

Abbreviated title :

Neuropathol. Appl. Neurobiol.

Volume number :

42

Pages :

194-209

Publication date :

2016-02-01

ISSN :

0305-1846

English keyword(s) :

granular osmiophilic material
cerebrovascular disease
clusterin
cerebral amyloid angiopathy
CADASIL
Alzheimer''s disease

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

OBJECTIVE: Brain clusterin is known to be associated with the amyloid-β deposits in Alzheimer's disease (AD). We assessed the distribution of clusterin immunoreactivity in cerebrovascular disorders, particularly focusing ...
Show more >OBJECTIVE: Brain clusterin is known to be associated with the amyloid-β deposits in Alzheimer's disease (AD). We assessed the distribution of clusterin immunoreactivity in cerebrovascular disorders, particularly focusing on white matter changes in small vessel diseases. METHODS: Post-mortem brain tissues from the frontal or temporal lobes of a total of 70 subjects with various disorders including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral amyloid angiopathy (CAA) and AD were examined using immunohistochemistry and immunofluorescence. We further used immunogold electron microscopy to study clusterin immunoreactivity in extracellular deposits in CADASIL. RESULTS: Immunostaining with clusterin antibodies revealed strong localization in arterioles and capillaries, besides cortical neurones. We found that clusterin immunostaining was significantly increased in the frontal white matter of CADASIL and pontine autosomal dominant microangiopathy and leukoencephalopathy subjects. In addition, clusterin immunostaining correlated with white matter pathology severity scores. Immunostaining in axons ranged from fine punctate deposits in single axons to larger confluent areas with numerous swollen axon bulbs, similar to that observed with known axon damage markers such as non-phosphorylated neurofilament H and the amyloid precursor protein. Immunofluorescence and immunogold electron microscopy experiments showed that whereas clusterin immunoreactivity was closely associated with vascular amyloid-β in CAA, it was lacking within the granular osmiophilic material immunolabelled by NOTCH3 extracelluar domain aggregates found in CADASIL. CONCLUSIONS: Our results suggest a wider role for clusterin associated with white matter damage in addition to its ability to chaperone proteins for clearance via the perivascular drainage pathways in several disease states.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
CNRS
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Submission date :

2019-11-27T13:37:24Z