Brain : a journal of neurology
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The two primary molecular pathologies in Alzheimer's disease are amyloid-β plaques and tau-immunoreactive neurofibrillary tangles. Investigations into these pathologies have been restricted to cerebrospinal fluid assays, and positron emission tomography tracers that can image amyloid-β plaques. Tau tracers have recently been introduced into the field, although the utility of the tracer and its relationship to other Alzheimer biomarkers are still unknown. ⋯ After controlling for levels of amyloid-β42, the correlations with tau uptake were r = 0.490 (P < 0.001) for t-tau and r = 0.492 (P < 0.001) for p-tau181 Within the cognitively normal cohort, levels of amyloid-β42, but not t-tau or p-tau181, were associated with elevated tracer binding that was confined primarily to the medial temporal lobe and adjacent neocortical regions. AV-1451 tau binding in the medial temporal, parietal, and frontal cortices is correlated with tau-related cerebrospinal fluid measures. In preclinical Alzheimer's disease, there is focal tauopathy in the medial temporal lobes and adjacent cortices.
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The tau tangle ligand (18)F-AV-1451 ((18)F-T807) binds to neuromelanin in the midbrain, and may therefore be a measure of the pigmented dopaminergic neuronal count in the substantia nigra. Parkinson's disease is characterized by progressive loss of dopaminergic neurons. Extrapolation of post-mortem data predicts that a ∼30% decline of nigral dopamine neurons is necessary to cause motor symptoms in Parkinson's disease. ⋯ In the subset of 12 patients, who also had a (123)I-FP-CIT scan, the mean total striatal dopamine transporter signal was decreased by 45% and the mean total (18)F-AV-1451 substantia nigra volume of distribution was decreased by 33% after median disease duration of 4.7 years (0.5-12.4 years). (18)F-AV-1451 positron emission tomography may be the first radiotracer to reflect the loss of pigmented neurons in the substantia nigra of parkinsonian patients. The magnitude of the nigral signal loss was smaller than the decrease in striatal dopamine transporter signal measured by dopamine transporter single photon emission computed tomography. These findings suggest a more severe loss of striatal nerve terminal function compared with neuronal cell bodies, in accordance with the post-mortem literature.
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Adrenomyeloneuropathy is the late-onset form of X-linked adrenoleukodystrophy, and is considered the most frequent metabolic hereditary spastic paraplegia. In adrenomyeloneuropathy the spinal cord is the main site of pathology. Differently from quantitative magnetic resonance imaging of the brain, little is known about the feasibility and utility of advanced neuroimaging in quantifying the spinal cord abnormalities in hereditary diseases. ⋯ A correlation between radial diffusivity and disease duration along the corticospinal tracts (r = 0.806, P < 0.01) was found. In conclusion, in adrenomyeloneuropathy patients quantitative magnetic resonance imaging-derived measures identify and quantify structural changes in the upper spinal cord and brain which agree with the expected histopathology, and suggest that the disease could be primarily caused by a demyelination rather than a primitive axonal damage. The results of this study may also encourage the employment of quantitative magnetic resonance imaging in other hereditary diseases with spinal cord involvement.
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Comparative Study
Increased cortical grey matter lesion detection in multiple sclerosis with 7 T MRI: a post-mortem verification study.
The relevance of cortical grey matter pathology in multiple sclerosis has become increasingly recognized over the past decade. Unfortunately, a large part of cortical lesions remain undetected on magnetic resonance imaging using standard field strength. In vivo studies have shown improved detection by using higher magnetic field strengths up to 7 T. ⋯ Sensitivity of 7 T magnetic resonance imaging was influenced by cortical lesion type: 100% for type I (T2), 11% for type II (FLAIR/T2), 32% for type III (T2*), and 68% for type IV (T2). We conclude that ultra-high field 7 T magnetic resonance imaging more than doubles detection of cortical multiple sclerosis lesions, compared to 3 T magnetic resonance imaging. Unfortunately, (subpial) cortical pathology remains more extensive than 7 T magnetic resonance imaging can reveal.
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Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus-cortical networks. ⋯ Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment.