The extent to which the tau tracer [18F]AV-1451 can differentiate between tauopathies is unknown. By comparing patients with Alzheimer’s disease and progressive supranuclear palsy (PSP), Passamonti et al. show that [18F]AV-1451 displays greater specificity for Alzheimer-related tau pathology than PSP-related pathology. A machine learning algorithm correctly diagnosed 94% of cases.

BackgroundThe prevalence of dementia with Lewy bodies (DLB) and dementia in Parkinson’s disease (PDD) in routine clinical practice is unclear. Prevalence rates observed in clinical and population-based cohorts and neuropathological studies vary greatly. Small sample sizes and methodological factors in these studies limit generalisability to clinical practice.MethodsWe investigated prevalence in a case series across nine secondary care services over an 18-month period, to determine how commonly DLB and PDD cases are diagnosed and reviewed within two regions of the UK.ResultsPatients with DLB comprised 4.6% (95% CI 4.0–5.2%) of all dementia cases. DLB was represented in a significantly higher proportion of dementia cases in services in the North East (5.6%) than those in East Anglia (3.3%; χ2 = 13.6, p < 0.01). DLB prevalence in individual services ranged from 2.4 to 5.9%. PDD comprised 9.7% (95% CI 8.3–11.1%) of Parkinson’s disease cases. No significant variation in PDD prevalence was observed between regions or between services.ConclusionsWe found that the frequency of clinical diagnosis of DLB varied between geographical regions in the UK, and that the prevalence of both DLB and PDD was much lower than would be expected in this case series, suggesting considerable under-diagnosis of both disorders. The significant variation in DLB diagnostic rates between these two regions may reflect true differences in disease prevalence, but more likely differences in diagnostic practice. The systematic introduction of more standardised diagnostic practice could improve the rates of diagnosis of both conditions.

ObjectiveWe tested whether in vivo neuroinflammation relates to the distinctive distributions of pathology in Alzheimer disease (AD) and progressive supranuclear palsy (PSP).MethodsSixteen patients with symptomatic AD (including amnestic mild cognitive impairment with amyloid-positive PET scan), 16 patients with PSP–Richardson syndrome, and 13 age-, sex-, and education-matched healthy controls were included in this case-control study. Participants underwent [11C]PK11195 PET scanning, which was used as an in vivo index of neuroinflammation.Results[11C]PK11195 binding in the medial temporal lobe and occipital, temporal, and parietal cortices was increased in patients with AD, relative both to patients with PSP and to controls. Compared to controls, patients with PSP showed elevated [11C]PK11195 binding in the thalamus, putamen, and pallidum. [11C]PK11195 binding in the cuneus/precuneus correlated with episodic memory impairment in AD, while [11C]PK11195 binding in the pallidum, midbrain, and pons correlated with disease severity in PSP.ConclusionsTogether, our results suggest that neuroinflammation has an important pathogenic role in the 2 very different human neurodegenerative disorders of AD and PSP. The increase and distribution of microglial activation suggest that immunotherapeutic strategies may be useful in slowing the progression of both diseases.

The role of inflammation in dementia with Lewy bodies is unclear. Surendranathan et al. report that microglial activation is elevated in mild disease, before decreasing as cognition declines. Inflammatory markers in the blood are also altered compared to control subjects, suggesting that inflammation could be targeted early in the disease.

IntroductionInflammation of the central nervous system is increasingly regarded as having a role in cognitive disorders such as dementia and depression, but it is not clear how such inflammation relates to other aspects of neuropathology, structural and functional changes in the brain and symptoms (as assessed via clinical and neuropsychological assessment and MRI). This study will explore these pathophysiological mechanisms using positron emission tomography (PET) which allows in vivo imaging of inflammation, amyloid and τ deposition, together with neuropsychological profiling, MRI and peripheral biomarker analysis.Methods and analysisUsing PET imaging of the ligand [11C]PK11195, we will test for increased neuroinflammation in vivo in patients with Alzheimer's disease, Lewy body dementia, frontotemporal dementia, progressive supranuclear palsy, late-onset depression and mild cognitive impairment, when compared to healthy controls. We will assess whether areas of inflammatory change are associated with amyloid and τ deposition (assessed using 11C-labelled Pittsburgh Compound B ([11C]PiB) and 18F-labelled AV-1451, respectively), as well as structural and connectivity markers found on MRI. Inflammatory biomarker analysis and immune-phenotyping of peripheral blood monocytes will determine the correlation between central inflammation and peripheral inflammation. Finally, we will examine whether central inflammatory markers seen on PET imaging are associated with global and domain specific cognitive impairments or predict cognitive decline over 12 months.Ethics and disseminationThe study protocol was approved by the local ethics committee, East of England—Cambridge Central Research Ethics Committee (reference: 13/EE/0104). The study is also Administration of Radioactive Substances Advisory Committee (ARSAC) approved as part of this process. Data will be disseminated by presentation at national and international conferences and by publication, predominantly in journals of clinical neuroscience, neurology and psychiatry.