Article Figures & Data
Figures
- Figure 1.
A, Schematic representation of the shape of the synaptic junctions: macular synapses with continuous disk-shaped PSD; perforated synapses with holes in the PSD; horseshoe-shaped with tortuous horseshoe-shaped perimeter with an indentation; and fragmented synapses with two PSDs with no connections between them. B, Proportion of macular, perforated, horseshoe-shaped, and segmented AS and SS in control cases and AD patients. In AD patients, fragmented synapses were significantly more frequent than in control cases (χ2, p < 0.001). C, Proportion of AS and SS belonging to each morphological category in control cases. The horseshoe-shaped synapses were significantly more frequent among SS than AS (χ2, p < 0.0001). D, Proportion of AS and SS belonging to each morphological category in AD cases. *** p < 0.001.
- Figure 2.
Serial images obtained by FIB/SEM from the human neuropil of Layer II of TEC. A, Low-magnification photograph showing a spine head, spine neck, and dendritic shaft in a single image. B−I, Selected sections (39–63) from an FIB/SEM stack of serial sections, to illustrate an AS targeting a spine head. Arrows (in B, I) indicate the beginning and the ending, respectively, of the synapse targeting a spine head. Scale bar, show in A, indicates 850 nm in A and 500 nm in B−I.
- Figure 3.
Screenshot of the EspINA software user interface. In the main window (top), the sections are viewed through the xy-plane (as obtained by FIB/SEM microscopy). The other two orthogonal planes, yz and xz, are also shown in adjacent windows (on the right). The 3D windows (bottom left) show the three orthogonal planes and the 3D reconstruction of segmented synapses. A 3D rectangular unbiased CF is shown on the bottom. The three acceptance planes are represented in green and three exclusion planes in red. Synapses inside the CF are colored in green and synapses outside the CF in red.
- Figure 4.
Representation of the distribution of AS (green) and SS (red) on spines and dendritic shafts. Percentages of each type are indicated. Synapses on spines have been sub-classified into those that are established on the head of the spine and those that are established on the neck. AS have been represented in green and SS in red. Control cases are represented on the top and AD patients on the bottom.
- Figure 5.
Schematic representation of single and multiple synapses on dendritic spine heads. Percentages of each type are indicated. Synapses on the necks and other combinations that were rarely found (<1%) have not been represented. AS have been represented in green and SS in red. Control cases are represented on the top and AD patients on the bottom.
- Figure 6.
Frequency histograms of the SAS area (A, B), perimeter (C, D), and curvature (E, F) of AS targeting spine heads, spine necks, and dendritic shafts from control cases (A, C, E) and from AD patients (B, D, F). The mean SAS curvature ratio of synapses targeting spine heads was significantly higher than in synapses targeting dendritic shafts (KW, p < 0.0001), both in control cases and AD patients.
- Figure 7.
Proportion of AS and SS on spines and dendritic shafts in control and AD cases. In AD patients, there is a significantly lower number of AS targeting spine heads (χ2, p < 0.001) and a significantly higher number of AS targeting dendritic shafts (χ2, p < 0.001). Data from SS shows no apparent differences between groups.
- Figure 8.
Frequency histograms of the SAS area (A, B), perimeter (C, D), and curvature (E, F) of macular, perforated, horseshoe-shaped and segmented AS from control cases (A, C, E) and from AD patients (B, D, F). The mean SAS area, perimeter and curvature of macular synapses was significantly smaller than in perforated, horseshoe-shaped and segmented synapses (KW, p < 0.0001), both in control cases and AD patients.
Tables
Patient Gender Age (years) Cause of death Postmortem delay (h) Braak stage CERAD stage Neuropsychological diagnosis AB1 Male 45 Lung cancer <1 NA NA NA AB2 Female 53 Pulmonary shock 4 NA NA NA IF10 Male 66 Bronchopneumonia plus cardiac failure 2 NA NA NA M16 Male 40 Traffic accident 3 NA NA NA M17 Male 36 Bronchopneumonia 2.5 NA NA NA IF1 Female 80 – 2 IV B No evidence of cognitive impairment and dementia IF2 Female 94 Pulmonary tuberculosis 1.5 V C Dementia IF6 Male 85 Pneumonia 2 III A Mild cognitive impairment VK11 Female 87 Respiratory inflammation 1.5 III−IV A Dementia VK22 Female 86 – 2 V C Dementia Braak Stages (Braak and Braak, 1991): III (NFTs in entorhinal cortex and closely related areas); III-IV (NFTs abundant in amygdala and hippocampus. Extending slightly into association cortex); V-VI (NFTs widely distributed throughout the neocortex and ultimately involving primary motor and sensory areas). CERAD Stages (Mirra et al., 1991): A (Low density of neuritic plaques); B (Intermediate density of neuritic plaques); C (High density of neuritic plaques). NA: Not applicable; NFTs: neurofibrillary tangles. – : Not available.
- Table 2.
Distribution of AS and SS on spines and dendritic shafts in control cases and AD patients
Group Type of synapse Synapses on spine heads Synapses on spine necks Synapses on aspiny dendritic shaft Synapses on spiny dendritic shaft Total synapses Control AS 59.1% (825) 0.5% (7) 19.9% (278) 20.5% (286) 100% (1396) SS 7.1% (8) 0.9% (1) 38.4% (43) 53.6% (60) 100% (112) Alzheimer AS 50.2% (579) 0.7% (8) 28.0% (323) 21.1% (243) 100% (1153) SS 8.8% (9) 1.0% (1) 41.2% (42) 49.0% (50) 100% (102) Synapses on spines have been sub-divided into those that are established on spine heads and those that are established on spine necks. Moreover, we differentiated between aspiny and spiny dendritic shafts. Data are expressed as percentages with the absolute number of synapses studied given in parentheses. Data for each individual case are represented in Table 2-1. Data expressed as absolute number of synapses were taken from this table to perform contingency tables showed in Table 2-2 and Table 2-3.
- Table 3.
Data regarding area (nm2), perimeter (nm), and curvature (ratio) of the SAS from synapses on spines and dendritic shafts in control cases and AD patients
Group Postsynaptic structure Type of synapse Area of SAS(nm2; mean ± SEM) Perimeter of SAS (nm; mean ± SEM) Curvature of SAS (mean ± SEM) Control Spine heads AS 14,5013 ± 4103 1877 ± 38 0.05 ± 0.001 SS 81,295 ± 12,011 1380 ± 138 0.05 ± 0.010 Spine necks AS 82,219 ± 23,461 1413 ± 255 0.04 ± 0.004 SS 19,199 ± 0 627.7 ± 0 0.04 ± 0 Dendritic shafts AS 115,703 ± 2845 1613 ± 24 0.04 ± 0.001 SS 76,129 ± 4299 1442 ± 51 0.06 ± 0.005 Alzheimer Spine heads AS 135,310 ± 4762 1815 ± 47 0.05 ± 0.002 SS 50,292 ± 12,137 1014 ± 128 0.06 ± 0.010 Spine necks AS 61,658 ± 13,211 1150 ± 119 0.05 ± 0.005 SS 55,339 ± 0 1269 ± 0 0.11 ± 0 Dendritic shafts AS 119,272 ± 3335 1638 ± 32 0.04 ± 0.001 SS 78,687 ± 5885 1280 ± 50 0.06 ± 0.005 All data are corrected for shrinkage factor. SEM: standard error of the mean.
- Table 4.
Proportion of the different shapes of synaptic junctions in control and AD patients
Group Type of synapse Macular synapses Perforated synapses Horseshoe-shaped synapses Fragmented synapses Total synapses Control AS 83.8% (2145) 11.8% (302) 3.8% (98) 0.6% (16) 100% (2561) SS 83.5% (106) 3.9% (5) 12.6% (16) 0.0% (0) 100% (127) Alzheimer AS 81.4% (1558) 11.5% (221) 5.3% (101) 1.8% (35) 100% (1915) SS 92.5% (110) 6.7% (8) 0.8% (1) 0.0% (0) 100% (119) Data are given as percentages with the absolute number of synapses studied in parentheses. Data for each individual case are represented in Table 4-1.
- Table 5.
Data regarding area (nm2), perimeter (nm), and curvature (ratio) of the SAS of macular, perforated, horseshoe-shaped, and fragmented synapses in control cases and AD patients
GroupShape of synapses Type of synapse Area of SAS
(nm2; mean ± SEM)Perimeter of SAS (nm; mean ± SEM) Curvature of SAS (mean ± SEM) Control Macular AS 88,272 ± 1283 1352 ± 11 0.04 ± 0.001 SS 70,960 ± 3764 1306 ± 40 0.05 ± 0.005 Perforated AS 264,960 ± 6606 2914 ± 58 0.07 ± 0.003 SS 108,320 ± 22,066 2080 ± 279 0.07 ± 0.016 Horseshoe-shaped AS 262,251 ± 13,757 3725 ± 163 0.09 ± 0.007 SS 88,466 ± 13204 1876 ± 153 0.06 ± 0.011 Fragmented AS 360,245 ± 34,068 3735 ± 435 0.14 ± 0.025 SS - - - Alzheimer Macular AS 91,162 ± 1689 1367 ± 14 0.04 ± 0.001 SS 59,436 ± 3156 1224 ± 42 0.06 ± 0.005 Perforated AS 259,540 ± 7942 2879 ± 73 0.07 ± 0.003 SS 123,147 ± 14,857 1776 ± 129 0.03 ± 0.006 Horseshoe-shaped AS 237,778 ± 9524 3568 ± 127 0.08 ± 0.006 SS 115,312 ± 0.0 2431 ± 0 0.07 ± 0.000 Fragmented AS 303,922 ± 21,783 2985 ± 210 0.13 ± 0.014 SS - - - All data are corrected for shrinkage factor. SEM: standard error of the mean.
Human TEC Striate cortex (area 17) of the monkey1 Visual cortex of the adult cat2 Somatosensory cortex of the adult rat (P60)3 Layer II Layer II−III All layers Layer II All layers All layers AS on spines 55.2% 54.9% 53.0% 71.2% 66.4% 73.0% AS on dendritic shafts 37.4% 27.7% 30.0% 13.3% 17.6% 12.9% SS on dendritic shafts 6.7% 11.4% 11.9% 10.8% 10.6% 9.3% SS on spines 0.61% 6.0% 5.1% 4.7% 5.3% 4.8% Data are given as percentages. Data were taken from: 1Beaulieu et al., 1992; 2Beaulieu and Colonnier (1985); 3Micheva and Beaulieu (1996).
Movies
- Movie 1.
Video of the EspINA software user interface. FIB/SEM sections are viewed through the xy-plane (as obtained by FIB/SEM microscopy) and yz- and xz-plane. 3D reconstruction of a perforated synapse is shown in the three orthogonal planes. This 3D reconstruction of one perforated synapse is shown in green at the end of the video. The 3D reconstruction of the synapse allows us to identify the morphology of the synapse as perforated.
Extended Data Table 2-1
Distribution of AS and SS on spines and dendritic shafts for each individual case Download Table 2-1, DOCX file.
Extended Data Table 2-2
An example of a 2 × 4 contingency table showing the type of synapse against the type of postsynaptic target in control cases Download Table 2-2, DOCX file.
Extended Data Table 2-3
Three examples of 2 × 2 contingency tables showing the type of synapse against the type of postsynaptic target in control cases Download Table 2-3, DOCX file.
Extended Data Table 4-1
Proportion of the different shapes of synaptic junctions for each case Download Table 4-1, DOCX file.
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