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IN VIVO BRAIN RECEPTOR OCCUPANCY FOR PDE‐10 RECEPTORS IN MICE AND RATS USING NON‐RADIOLABELED TRACER
Author(s) -
Bhyrapuneni Gopinadh,
Thentu Jagadeesh Babu,
Boggavarapu Rajesh,
Padala Nagasurya Prakash,
Khan Imran,
Ajjala Devender Reddy,
Rasheed Mohammed Abdul,
Nirogi Ramakrishna
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.1098
Subject(s) - receptor , pharmacology , striatum , in vivo , chemistry , neuroscience , biology , medicine , dopamine , microbiology and biotechnology
Background:Archival neuropathologicmaterialmayprove to bevery useful andmay significantly aid the neurologist in the diagnosis of hereditary neurodegenerative disease. The fixed and paraffin embedded brain tissue of a 33year-old woman has been studied and archived since 1991. The proband’s son presented with neurological signs 22 years after the proband’s death. Methods: Clinical and family reports detailing the evolution of the proband’s illness were available. Neuropathologic studies of the brain, postmortem, had been carried out using histological methods including hematoxylin and eosin with Luxol fast blue (H&E/LFB), Bielschowsky and Thioflavin S. For immunohistochemistry, antibodies against tau, and amyloid beta (Ab) were used. DNA could not be extracted from fixed tissue, but was obtained from the 27-year-old son of the proband. Results:While in high school, the proband showed forgetfulness, loss of coordination and some trouble walking. During college, she required tutoring. At age 28, following the birth of her first child, she became progressively ataxic. By age 30, she was no longer able towalk without the aid of a walker. She had difficulty in speaking and swallowing. Neurologic exam at age 31 showed severe spastic and ataxic gait and significant memory loss. Extensive diagnostic work-up was negative. A magnetic resonance imaging study revealed decreased signal in the putamen and globus pallidus. Multiple sclerosis, spinocerebellar degeneration and Hallervorden-Spatz disease were considered as possible diagnoses. The patient deteriorated rapidly and died at the age of 33. Three neuropathologists, independently, diagnosed the proband as having been affected by Alzheimer disease. The 27-year-old proband’s son presented with hyperreflexia, dysarthria, and gait abnormalities. Molecular genetic analysis revealed anATG>GTGpoint mutation predicting an amino acid substitution of methionine to valine (M233V) in the PSEN1 gene. Conclusions: Considering the similarity of the clinical presentation and the age of onset of symptoms in the proband and her son, we hypothesize that both individuals have the PSEN1 M233V mutation and that the son is in the very early stage of familial Alzheimer disease. The data from the archival tissue contributed significantly to direct toward a diagnosis and a potential therapeutic interventions for the proband’s son. Funding source: P30AG010133.