2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Diabetes-Mellitus--Type-2

Type 2 diabetes mellitus (DM) has been shown to increase the risk for cognitive decline and dementia, such as Alzheimer disease (AD) and vascular dementia (VaD). In addition to AD and VaD, there may be a dementia subgroup associated with specific DM-related metabolic abnormalities rather than AD pathology or cerebrovascular disease, referred to as diabetes-related dementia (DrD).. We studied 11C-PiB and 11C-PBB3 positron emission tomography (PET) in 31 subjects with DrD and 5 subjects with AD associated with DM to assess amyloid and tau deposits in the brain.. All subjects with AD showed both positive PiB and PBB3. However, only 12 out of 31 subjects (39%) with DrD showed positive PiB, whereas 17 out of 21 subjects (81%) who underwent PBB3 PET showed positive PBB3. Depending on the positivity of PiB and PBB3, we classified 21 subjects into a negative PiB and a positive PBB3 pattern (11 cases, 52%), indicating tauopathy, a positive PiB and a positive PBB3 pattern (6 cases, 29%), indicating AD pathology, or a negative PiB and a negative PBB3 pattern (4 cases, 19%). Among 11 subjects showing a negative PiB and a positive PBB3 pattern, there were 2 PBB3 deposit patterns, including the medial temporal lobe only and extensive neocortex beyond the medial temporal lobe.. DrD showed variable amyloid and tau accumulation patterns in the brain. DrD may be associated predominantly with tau pathology, in addition to AD pathology and non-amyloid/non-tau neuronal damage due to DM-related metabolic abnormalities.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid; Aniline Compounds; Benzothiazoles; Dementia; Diabetes Mellitus, Type 2; Female; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Positron-Emission Tomography; Psychiatric Status Rating Scales; tau Proteins; Thiazoles; Tomography, Emission-Computed, Single-Photon

Gadolinium-based nanoparticles were functionalized with either the Pittsburgh compound B or a nanobody (B10AP) in order to create multimodal tools for an early diagnosis of amyloidoses.. The ability of the functionalized nanoparticles to target amyloid fibrils made of β-amyloid peptide, amylin or Val30Met-mutated transthyretin formed in vitro or from pathological tissues was investigated by a range of spectroscopic and biophysics techniques including fluorescence microscopy.. Nanoparticles functionalized by both probes efficiently interacted with the three types of amyloid fibrils, with K. Such functionalized nanoparticles could represent promising flexible and multimodal imaging tools for the early diagnostic of amyloid diseases, in other words, Alzheimer's disease, Type 2 diabetes mellitus and the familial amyloidotic polyneuropathy.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Animals; Brain; Diabetes Mellitus, Type 2; Gadolinium; Humans; Immunohistochemistry; Islet Amyloid Polypeptide; Mice; Multimodal Imaging; Nanoparticles; Plaque, Amyloid; Single-Domain Antibodies; Thiazoles

To determine the effects of Type 2 diabetes (DM2) on levels of brain amyloidosis and cognition in a community-dwelling cohort of nondemented elderly individuals.. 33 subjects (16 DM2, 17 nondiabetic) were prospectively recruited. Subjects underwent a PET scan using the amyloid tracer, Pittsburgh Compound B, and a neuropsychological evaluation. Associations between DM2, brain amyloidosis, and cognition were assessed using multivariate regressions, adjusting for age and APOE4 status.. DM2 subjects had lower global cognitive function (p=0.018), as measured by the Repeatable Battery for the Assessment of Neuropsychological Status. There was no difference in brain amyloidosis between groups (p=0.25).. Community-dwelling, nondemented individuals with DM2 had greater cognitive deficits, which do not appear to be mediated by brain amyloidosis. Further studies exploring potential mediators of these cognitive deficits should be performed.

Topics: Aged; Amyloidosis; Aniline Compounds; Brain; Case-Control Studies; Cognition Disorders; Diabetes Mellitus, Type 2; Female; Humans; Independent Living; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Thiazoles