Muscarinic acetylcholine receptor status in Alzheimer’s disease assessed using (R, R) 123I-QNB SPECT

Institute for Ageing and Health, Newcastle University, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, UK.
Journal of Neurology (Impact Factor: 3.38). 07/2007; 254(7):907-13. DOI: 10.1007/s00415-006-0473-8
Source: PubMed


One of the most characteristic changes in Alzheimer's disease (AD) is a deficit in cortical cholinergic neurotransmission and associated receptor changes.
To investigate differences in the distribution of M1/M4 receptors using (R, R) (123)I-iodo-quinuclidinyl-benzilate (QNB) and single photon emission computed tomography (SPECT) in patients with mild/moderate AD and age-matched controls. Also, to compare (123)I-QNB uptake to the corresponding changes in regional cerebral blood flow (rCBF) in the same subjects.
Forty two subjects (18 AD and 24 healthy elderly controls) underwent (123)IQNB and perfusion (99m)Tc-exametazime SPECT scanning. Image analysis was performed using statistical parametric mapping (SPM99) following intensity normalisation of each image to its corresponding mean whole brain uptake. Group differences and correlations were assessed using two sample t-tests and linear regression respectively.
Significant reductions in (123)I-QNB uptake were observed in regions of the frontal rectal gyrus, right parahippocampal gyrus, left hippocampus and areas of the left temporal lobe in AD compared to controls (height threshold of p < or = 0.001 uncorrected). Such regions were also associated with marked deficits in rCBF. No significant correlations were identified between imaging data and clinical variables.
Functional impairment as measured by rCBF is more widespread than changes in M1/M4 receptor density in mild/moderate AD, where there was little or no selective loss of M1/M4 receptors in these patients that was greater than the general functional deficits shown on rCBF scans.

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    • "For example, previous studies used a different biochemical approach to assessed global M1 binding sites (Araujo et al., 1988) and different clinical and neuropathological criteria (Araujo et al., 1988; Aubert et al., 1992). Variability in methodology and patient populations reported in the literature are similar to inconsistencies found between muscarinic neuroimaging studies evaluating both muscarinic function and density in AD (Holman, et al., 1985; Weinberger, et al., 1991; Brown, et al., 2003; Kemp, et al., 2003; Pakrasi, et al., 2007). Moreover, interpretation derived from previous postmortem tissue studies are tempered by the fact that many of the procedures used have not been validated for their ability to selectively detect M 1 receptors and may include measurement of additional muscarinic receptor subtypes. "
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