ABSTRACT
INTRODUCTION: Metabotropic glutamate receptors play a critical role in the pathogenesis of Alzheimer's disease due to their involvement in processes of memory formation, neuroplasticity, and synaptotoxity. The objective of the current study was to study mGluR5 availability measured by [11 C]-ABP688 (ABP) in patients with clinically diagnosed Alzheimer's dementia (AD). METHODS: A bolus-infusion protocol of [11 C]-ABP688 was applied in 9 subjects with AD and 10 cognitively healthy controls (Controls) to derive distribution volume estimates of mGluR5. Furthermore, we also estimated cerebral perfusion by averaging early frame signal of initial ABP bolus injection. RESULTS: Subjects with Alzheimer's dementia (mean age: 77.3/SD 5.7) were older than controls (mean age: 68.5/SD: 9.6) and scored lower on the MMSE (22.1/SD2.7 vs. 29.0/SD0.8). There were no overall differences in ABP signal. However, distribution volume ratio (DVR) for ABP was reduced in the bilateral hippocampus (AD: 1.34/SD: 0.40 vs. Control: 1.84/SD:0.31, p = .007) and the bilateral amygdala (AD:1.86/SD:0.26 vs. Control:2.33/SD:0.37 p = .006) in AD patients compared to controls. Estimate of cerebral blood flow was reduced in the bilateral hippocampus in AD (AD:0.75/SD:0.10 vs. Control:0.86/SD:0.09 p = .02). CONCLUSION: Our findings demonstrate reduced mGluR5 binding in the hippocampus and amygdala in Alzheimer's dementia. Whether this is due to synaptic loss and/or consecutive reduction of potential binding sites or reflects disease inherent mechanisms remains to be elucidated in future studies.
Subject(s)
Alzheimer Disease , Aged , Alzheimer Disease/diagnostic imaging , Amygdala/diagnostic imaging , Brain , Carbon Radioisotopes , Hippocampus/diagnostic imaging , Humans , Oximes , Positron-Emission Tomography , PyridinesSubject(s)
D-Amino-Acid Oxidase/genetics , Genetic Variation , Schizophrenia/genetics , Base Sequence , DNA Primers , Female , Humans , Male , Schizophrenia/enzymologyABSTRACT
BACKGROUND/AIMS: Subjective memory impairment (SMI) has been suggested as a manifestation of Alzheimer's Disease (AD) preceding mild cognitive impairment (MCI). In this study, we determined the volumes of the hippocampus, the entorhinal cortex (EC) and the amygdala to provide biological evidence for AD in SMI. METHODS: Regional volumetric measures were manually traced on 3-Tesla MRI scans. RESULTS: Total brain volume did not differ between the groups. Individuals with SMI had reduced volumes of the hippocampus bilaterally (right p = 0.001; left p < 0.001), the bilateral EC (right p = 0.031, left p = 0.006) and the right amygdala (p = 0.01) compared to the control group. CONCLUSION: Volume reduction of bilateral hippocampus, bilateral EC and right amygdala supports the concept of SMI as a very early manifestation of AD prior to MCI. SMI may indicate awareness of a degenerative process that can still be functionally compensated.
Subject(s)
Memory Disorders/pathology , Temporal Lobe/pathology , Aged , Amygdala/pathology , Apolipoproteins E/genetics , Brain/pathology , Education , Entorhinal Cortex/pathology , Female , Functional Laterality/physiology , Hippocampus/pathology , Humans , Magnetic Resonance Imaging , Male , Memory Disorders/psychology , Middle Aged , Neuropsychological Tests , Psychiatric Status Rating ScalesABSTRACT
Recently, an association of the Val66Met polymorphism of the brain-derived neurotrophic factor with hippocampal volume in patients with major depression has been reported. Here, we aimed at replicating this finding in an independent German sample. We included 79 patients with unipolar major depressive episodes and 84 healthy comparison participants. The brain-derived neurotrophic factor Val66Met polymorphism was determined in all participants. The volume of the hippocampus was manually traced on high-resolution magnetic resonance images. The hippocampal volumes of patients were significantly smaller than those of the comparison participants, confirming previous reports. There was, however, no Val66Met effect on hippocampal volume in either group. To conclude, we did not replicate the Val66Met effect on hippocampal volume in neither patients with major depression nor in healthy participants.
Subject(s)
Amino Acid Substitution/genetics , Brain-Derived Neurotrophic Factor/genetics , Depressive Disorder, Major/genetics , Depressive Disorder, Major/pathology , Genetic Predisposition to Disease , Hippocampus/pathology , Polymorphism, Single Nucleotide/genetics , Adult , Aged , Case-Control Studies , Female , Humans , Male , Methionine/genetics , Middle Aged , Organ Size , Valine/genetics , Young AdultABSTRACT
The proline dehydrogenase locus must be considered as a positional and functional candidate in schizophrenia. It is located in the chromosomal region of the velocardiofacial syndrome on 22q11 that is suspected to contain genes relevant to schizophrenia, and is involved in the metabolism of neurotransmitters. Positive association between single-nucleotide polymorphisms at the proline dehydrogenase locus and schizophrenia further supported the role of proline dehydrogenase in the development of schizophrenia. In order to replicate these findings, we analyzed three single-nucleotide polymorphisms in a sample comprising 299 schizophrenic patients and 300 controls. In addition, we assessed whether proline dehydrogenase also contributes to bipolar affective disorder, because chromosome 22q11 is also implicated in bipolar affective disorder. We therefore included 300 patients with bipolar affective disorder. This is the first study on a potential involvement of the proline dehydrogenase locus in bipolar affective disorder. Neither single marker nor haplotype analysis revealed an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder.