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Flow cytometry analysis of synaptosomes from post-mortem human brain reveals changes specific to Lewy body and Alzheimer's disease
- Source :
- Laboratory investigation; a journal of technical methods and pathology
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Synaptic dysfunction is thought to play an important role in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s disease (AD) and Lewy body disease (LBD). To improve our understanding of synaptic alterations in health and disease, we investigated synaptosomes prepared from post-mortem human cerebral cortex, putamen, and two regions of the caudate nucleus, dorso-lateral (DL) and ventro-medial (VM), regions commonly affected in AD and LBD. We observed that the fraction of synaptosomal particles with reactivity for dopamine transporter (DAT) was significantly reduced in the putamen and VM caudate of patients with neuropathological diagnosis of LBD. As expected, these differences also were reflected in direct measurements of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in caudate and putamen of LBD patients. The fraction of synaptosomal particles positive for amyloid β (Aβ) was significantly increased in frontal cortical samples of patients with the neuropathological diagnosis of severe AD, and was positively correlated with disease progression. We also prepared synaptosomes from the striatum of mice with severe loss of DA neurons (Slc6a3-DTR mice) and wild-type littermate controls. We observed dramatically reduced levels of DAT-positive synaptosomes in Slc6a3-DTR mice following exposure to diphtheria toxin (DT). Striatal levels of DA and DOPAC in Slc6a3-DTR mice also were reduced significantly following DT exposure. We conclude that flow cytometric analysis of synaptosomes prepared from human or mouse brain provides an opportunity to study expression of pathology-associated proteins and also the specific loss of dopaminergic nerve terminals. Hence, we believe it is a valid method to detect pathological changes at the level of the synapse in LBD as well as AD.
- Subjects :
- Lewy Body Disease
Male
medicine.medical_specialty
Pathology
striatum
Caudate nucleus
Striatum
Article
Pathology and Forensic Medicine
Mice
Catecholamines
Alzheimer Disease
Internal medicine
Synaptosome
medicine
Animals
Humans
Molecular Biology
Dopamine transporter
Aged, 80 and over
Dopamine Plasma Membrane Transport Proteins
Amyloid beta-Peptides
biology
Lewy body
Putamen
Dopaminergic
Brain
Cell Biology
Human brain
Flow Cytometry
medicine.disease
3. Good health
amyloid beta
cortex
medicine.anatomical_structure
Endocrinology
nervous system
Cerebral cortex
Vesicular Glutamate Transport Protein 1
alpha-Synuclein
biology.protein
Female
dopamine
Alzheimer’s disease
Synaptosomes
dementia
Subjects
Details
- ISSN :
- 00236837
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Laboratory Investigation
- Accession number :
- edsair.doi.dedup.....7b66b87662b543e44a71b020afef8001