Altered Sphingolipid Balance in Capillary Cerebral Amyloid Angiopathy.
J Alzheimers Dis
; 60(3): 795-807, 2017.
Article
en En
| MEDLINE
| ID: mdl-27662305
ABSTRACT
BACKGROUND:
The majority of patients with Alzheimer's disease (AD) exhibit amyloid-ß (Aß) deposits at the brain vasculature, a process referred to as cerebral amyloid angiopathy (CAA). In over 51% of AD cases, Aß also accumulates in cortical capillaries, which is termed capillary CAA (capCAA). It has been postulated that the presence of capCAA in AD is a specific subtype of AD, although underlying mechanisms are not yet fully understood. Sphingolipids (SLs) are implicated in neurodegenerative disorders, including AD. However, to date it remains unknown whether alterations in the SL pathway are involved in capCAA pathogenesis and if these differ from AD.OBJECTIVE:
To determine whether AD cases with capCAA have an altered SL profile compared to AD cases without capCAA.METHODS:
Immunohistochemistry was performed to assess the expression and localization of ceramide, acid sphingomyelinase (ASM), and sphingosine-1-phosphate receptors (S1P1, S1P3). In addition, we determined the concentrations of S1P as well as different chain-lengths of ceramides using HPLC-MS/MS.RESULTS:
Immunohistochemical analysis revealed an altered expression of ceramide, ASM, and S1P receptors by reactive astrocytes and microglial cells specifically associated with capCAA. Moreover, a shift in the balance of ceramides with different chain-lengths and S1P content is observed in capCAA.CONCLUSION:
Here we provide evidence of a deregulated SL balance in capCAA. The increased levels of ASM and ceramide in activated glia cells suggest that the SL pathway is involved in the neuroinflammatory response in capCAA pathogenesis. Future research is needed to elucidate the role of S1P in capCAA.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Esfingolípidos
/
Capilares
/
Angiopatía Amiloide Cerebral
/
Enfermedad de Alzheimer
/
Lóbulo Occipital
Límite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Países Bajos