Immunolocalization of 14-3-3 proteins in Alzheimer's disease (AD) brains was investigated using isoform-specific antibodies. Weak granular immunoreactivity of 14-3-3 proteins was found in neuronal cytoplasm in control subjects and AD brains. Both intracellular and extracellular neurofibrillary tangles (NFTs), as well as neuropil thread-like structures, were immunopositive for 14-3-3 proteins. This was corroborated by triple-fluorolabeling method visualizing paired helical filament (PHF) tau and 14-3-3 epitopes in relation to fibrillary state detected by thiazin red. Pretangle neurons (positive for PHF-tau without fibrillary structure detected by thiazin red) only contained fine granular immunoreactivity (IR) of 14-3-3, which was similarly found in unaffected neurons. Granular cytoplasmic IR of 14-3-3 proteins in pretangle neurons was not colocalized to granular tau-like IR, which suggests that participation of 14-3-3 proteins in NFT formation was restricted to its later stages. Its zeta isoform was most prominent in these NFTs, suggesting that this isoform is a major component involved in the formation of NFTs. In contrast, IR of epsilon isoform was found in the neuropil of the hippocampus and that of sigma isoform was localized to granule cells of the dentate gyrus in AD brains, as seen in the age-matched controls. Expression of 14-3-3 proteins were found to be highly variable and dependent on their isoforms, regions and cell types. Molecular, as well as topographical, dissection of 14-3-3 proteins will provide us with an improved understanding of this molecule in normal and pathological conditions.

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Purpose123I-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) dopamine transporter single photon emission computed tomography (DAT SPECT) and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy can be used to assist in the diagnosis of patients with dementia with Lewy bodies (DLB). We compared the diagnostic value of these two methods in differentiating DLB from Alzheimer’s disease (AD). Furthermore, we evaluated whether a combination of DAT SPECT and MIBG myocardial scintigraphy would provide a more useful means of differentiating between DLB and AD.MethodsPatients with AD (n = 57) and patients with DLB (n = 76) who underwent both DAT SPECT and MIBG myocardial scintigraphy were enrolled. The sensitivity, specificity, and accuracy of both methods as well as their combination for differentiating DLB from AD were calculated. Moreover, we examined whether symptoms of the patients with DLB were associated with the patterns of the abnormalities displayed on DAT SPECT and MIBG myocardial scintigraphy.ResultsThe sensitivity and specificity of differentiating DLB from AD were 72.4 and 94.4 % by the heart to mediastinum ratio of MIBG uptake, 88.2 and 88.9 % by the specific binding ratio on DAT SPECT, and 96.1 and 90.7 % by their combination, respectively. The combined use of DAT SPECT and MIBG myocardial scintigraphy enabled more accurate differentiation between DLB and AD compared with either DAT SPECT or MIBG myocardial scintigraphy alone. There was a significantly higher frequency of parkinsonism in the abnormal DAT SPECT group than the normal DAT SPECT group. On the other hand, there was a higher frequency of the appearance of rapid eye movement (REM) sleep behavior disorder in the abnormal MIBG uptake group than the normal MIBG uptake group.ConclusionThese results suggested that using a combination of these scintigraphic methods is a useful and practical approach to differentiate DLB from AD.

Providing education to caregivers of patients with dementia improves their depression symptoms and sense of burden, and tends to improve the behaviour and psychological symptoms of dementia in the patients. Providing education to caregivers of dementia patients may hence result in beneficial effects for both the patients and their caregivers, and should be widely used in dementia care.