Imaging Studies of Aging, Neurodegenerative Disease, and Alcoholism.

Neurodegenerative diseases such as Alzheimers disease, disorders such as alcoholism, and the aging process can lead to impaired cognitive function and dementia. Researchers and clinicians have used noninvasive imaging techniques to determine the structural and physiological alterations in the brain that are associated with these conditions. Analyses of the brains structure have found that shrinkage (atrophy) of the brain tissue is characteristic for all conditions associated with dementia, but that the specific locations of atrophied brain structures vary among different neurodegenerative diseases and alcohol-induced disorders. Similarly, studies analyzing the metabolism in various brain structures have found that, depending on whether dementia was induced by neurodegenerative diseases, alcoholism, or aging, the affected brain structures vary slightly. Based on such studies, researchers and clinicians now can more accurately define different types of dementia and predict their clinical course

GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop

The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.Peer reviewe

Imaging Studies of Aging, Neurodegenerative Disease, and Alcoholism.

Neurodegenerative diseases such as Alzheimer's disease, disorders such as alcoholism, and the aging process can lead to impaired cognitive function and dementia. Researchers and clinicians have used noninvasive imaging techniques to determine the structural and physiological alterations in the brain that are associated with these conditions. Analyses of the brain's structure have found that shrinkage (atrophy) of the brain tissue is characteristic for all conditions associated with dementia, but that the specific locations of atrophied brain structures vary among different neurodegenerative diseases and alcohol-induced disorders. Similarly, studies analyzing the metabolism in various brain structures have found that, depending on whether dementia was induced by neurodegenerative diseases, alcoholism, or aging, the affected brain structures vary slightly. Based on such studies, researchers and clinicians now can more accurately define different types of dementia and predict their clinical course

Imaging studies of aging, neurodegenerative disease, and alcoholism

Neurodegenerative diseases such as Alzheimer's disease, disorders such as alcoholism, and the aging process can lead to impaired cognitive function and dementia. Researchers and clinicians have used noninvasive imaging techniques to determine the structural and physiological alterations in the brain that are associated with these conditions. Analyses of the brain's structure have found that shrinkage (atrophy) of the brain tissue is characteristic for all conditions associated with dementia, but that the specific locations of atrophied brain structures vary among different neurodegenerative diseases and alcoholinduced disorders. Similarly, studies analyzing the metabolism in various brain structures have found that, depending on whether dementia was induced by neurodegenerative diseases, alcoholism, or aging, the affected brain structures vary slightly. Based on such studies, researchers and clinicians now can more accurately define different types of dementia and predict their clinical course. KE

PET 6-[F]fluoro-L-m-tyrosine Studies of Dopaminergic Function in Human and Nonhuman Primates.

Although positron emission tomography (PET) and the aromatic L-amino acid decarboxylase (AADC) tracer 6-[(18)F]fluoro-L-m-tyrosine (FMT) has been used to assess the integrity of the presynaptic dopamine system in the brain, relatively little has been published in terms of brain FMT uptake values especially for normal human subjects. Twelve normal volunteer subjects were scanned using PET and FMT to determine the range of normal striatal uptake values using Patlak graphical analysis. For comparison, seven adult rhesus monkeys were studied and the data analyzed in the same way. A subset of monkeys that were treated with a unilateral intracarotid artery infusion of the dopamine neurotoxin MPTP showed an 87% decrease in striatal FMT uptake. These findings support the use of PET and FMT to image AADC distribution in both normal and diseased brains using Patlak graphical analysis and tissue input functions

Functional Effects of AAV2-GDNF on the Dopaminergic Nigrostriatal Pathway in Parkinsonian Rhesus Monkeys

We investigated the safety and neuroregenerative potential of an adeno-associated virus (AAV2) containing human glial cell line-derived neurotrophic factor (GDNF) in an MPTP primate model of Parkinson's disease. Dopaminergic function was evaluated by positron emission tomography with 6-[18F]fluoro-l-m-tyrosine (FMT) before and after AAV2-GDNF or phosphate-buffered saline infusion bilaterally into the putamen. FMT uptake was significantly increased bilaterally in the putamen of AAV2-GDNF but not phosphate-buffered saline-treated animals 6 months after infusion, indicating increased dopaminergic activity in the nigrostriatal pathways. AAV2-GDNF-treated animals also showed clinical improvement without adverse effects. These findings are consistent with our previous report in aged nonhuman primates that showed evidence of enhanced use of striatal dopamine and dopaminergic nigrostriatal innervation. Clinical improvement and evidence of functional recovery in the nigrostriatal pathway, and the absence of adverse effects, support the safety of this approach for the delivery of GDNF over a 6-month period