Article Figures & Data
Figures
- Fig. 1.
Chemical structures of thioflavin-T and BTA-1. The uncharged compound, BTA-1, differs from thioflavin-T by the lack of three methyl groups, including the methyl group imparting the positive charge to the quaternary heterocyclic nitrogen of thioflavin-T (arrow).
- Fig. 2.
Paraffin sections (8 μm) from AD brain stained with 100 nm BTA-1. Left panel shows plaques and cerebrovascular amyloid in the frontal cortex. Right panel shows plaques and neurofibrillary tangles in the entorhinal cortex. Scale bar, 100 μm. Most smaller bright spots are residual lipofuscin autofluorescence.
- Fig. 3.
A, Comparison of [3H]BTA-1 binding to homogenates from control (open bars, circles), AD (filled bars, squares), and NAD brain (hatched bars, triangles) frontal gray (Fr) or cerebellum (Cb).B, Ratio of [3H]BTA-1 binding to the Fr and Cb for each individual brain. Bars represent the mean, and error bars represent the SD. Also shown are the individual data points.
- Fig. 4.
Scatchard plots showing the binding of [3H]BTA-1 to homogenates from AD frontal gray matter (▪) and underlying frontal white matter from the same AD brain (▵). In this AD frontal gray matter homogenate, theKd was 4.4 nm and theBmax was 6.9 pmol/mg wet weight. In the frontal white matter immediately underlying this gray matter sample, the Kd was 111 nm and theBmax was 27 pmol/mg wet weight. Also shown is a Scatchard plot showing the binding of [3H]BTA-1 to a homogenate from control brain frontal gray (○) in which the Kd was 180 nm and the Bmax was 5.9 pmol/mg wet weight.
- Fig. 5.
Paraffin sections (8 μm) from the entorhinal cortex (A, B), frontal cortex (C, D), and cerebellum (E,F) of a Braak stage II control brain (A, C, E, Cntl 04) and a Braak stage VI AD brain (B,D, F, AD 01) stained with X-34. X-34 is a highly sensitive, fluorescent Congo red derivative that intensely stains plaques, NFTs, and amyloid deposits in general (Styren et al., 2000). Marked atrophy of AD tissue was notable in all regions. In the entorhinal cortex of the control subject (A), frequent numbers of NFTs were seen, whereas there were no amyloid deposits. In the AD case (B), there also were frequent NFTs along with diffuse amyloid deposits (arrows). X-34-positive NFTs and amyloid plaques were absent from the frontal cortex of the control case (C), whereas they were abundant in AD (D). There was no detectable X-34 staining of plaques or NFT in control (E) and AD (F) cerebellum. Control frontal cortex (C) and cerebellum from both control and AD (E, F) show small stellate cells that stain with X-34. Scale bar, 200 μm.
- Fig. 6.
Comparison of the Kivalues of 10 BTA-1 derivatives for inhibition of [3H]BTA-1 binding to Aβ(1–40) fibrils and homogenates of AD frontal gray (filled diamonds,solid line). Also shown is a comparison of the same data for Aβ(1–40) fibrils compared with Kivalues previously determined in a separate, older lot of Aβ(1–40) fibrils (open squares, dashed line).
Tables
Brain no. Primary neuropath Dx Other neuropath Dx Braak stage Cortical NP1-a Age PMI (hr) AD 01 AD1-a AA (severe) VI Frequent 83 3 AD 02 AD1-a AA (severe) VI Frequent 57 4 AD 03 AD1-a AA (mild) VI Frequent 78 3 AD 04 AD1-a AA (mild), DLB (1/10)1-b VI Frequent 80 4 AD 05 AD1-a AA (moderate) VI Frequent 78 9 AD 06 AD1-a Chronic subdural hematoma IV Frequent 85 3 AD 07 AD1-a AA (severe), old infarct right putamen VI Frequent 79 4 AD 08 AD1-a AA (mild), old infarct left basis pontis IV Frequent 83 4 AD 09 AD1-a Infarcts, right putamen (3 old);
Left thalamus (1 subacute)IV Frequent 84 4 Average: 78.6 4.2 SD 8.5 1.9 Cntl 01 Normal brain1-a Moderate atherosclerosis, circle of Willis 0 None 72 18 Cntl 02 Normal brain1-a Persistent posterior fetal circulation, bilaterally
Incidental choroid plexus cystI None 82 4 Cntl 03 Normal brain1-a Moderate congestion of leptomeninges 0 None 75 8 Cntl 04 Normal brain1-a Incidental focal hypoplasia of corpus callosum II None 82 3 Cntl 05 Normal brain1-a None I None 74 5 Cntl 06 Normal brain1-a Atherosclerosis, circle of Willis
Old infarcts cerebellar cortex, inferior olivary nucleusII Rare 72 4 Cntl 07 Normal brain1-a Subacute infarct right brainstem I None 74 6 Cntl 08 Normal brain1-a None 0 None 53 5 Average: 73.0 6.6 SD 9.0 4.8 p = (vs AD) 0.21 0.22 NAD 01 Pure DLB(7/10)1-b None I None 69 10 NAD 02 Huntington's Status post evacuation subdural hematoma,
Atherosclerosis, circle of WillisI None 64 7 NAD 03 Pick's Atherosclerosis, circle of Willis 0 None 66 4 NAD 04 MND-inclusion
DementiaSevere cortical atrophy, atherosclerosis, circle of Willis 0 None 75 8 NAD 05 DLDHF Mesial temporal sclerosis I None 56 4 NAD 06 DLB(6/10)1-b Parkinson's disease I None 87 8 Average: 69.5 6.8 SD 10.6 2.4 p= (vs AD) 0.11 0.05 NP, Neuritic plaques; PMI, postmortem interval; AD, Alzheimer's disease; AA, amyloid angiopathy; DLB, dementia with Lewy Bodies; SD, standard deviation; p = (vs AD), p values compared with corresponding values for AD cases; Cntl, control; NAD, demented, non-Alzheimer's disease; MND, motor neuron disease-inclusion dementia (Jackson et al., 1996); DLDHF, dementia lacking distinctive histologic features (Mann, 1998); neuropath; Dx, neuropathological diagnosis.
↵F1-a CERAD criteria (Mirra et al., 1991).
↵F1-b Scored according to consensus criteria (McKeith et al., 1996).
- Table 2.
[3H]BTA-1 binding to specified areas of a Braak stage II control brain (Cntl 04) and a Braak stage VI AD brain (AD 01)
Brain area pmol BTA-1/mg wet weight (mean ± SD) p value2-a Cntl 04 AD 01 EC 0.078 ± 0.006 0.082 ± 0.008 0.489 Fr 0.093 ± 0.004 0.887 ± 0.011 0.00001 Cb 0.078 ± 0.0001 0.043 ± 0.004 0.005 See Table 1 for details. EC, Entorhinal cortex; Fr, frontal cortex; Cb, cerebellum.
↵F2-a Student's t test comparison of control and AD values.
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