Table 1.
Study type/ Neuronal subtype | Model/Group of study | Functional phenotype | Methodology | Reference |
---|---|---|---|---|
Human studies | ||||
Clinical study | 16 non-demented APOE4 carriers (two APOE4/4 and 14 APOE3/4 subjects) | Increased activity of parahippocampal, left hippocampal, parietal, temporal, and prefrontal regions of APOE4 carriers | fMRI | [18] |
14 non-demented APOE3/3 individuals | ||||
Clinical study | Ten controls | Increased hippocampal activity in MCI individuals compared to controls | fMRI | [9] |
Nine mild MCI patients | Decreased hippocampal and entorhinal activity in AD patients compared to controls | |||
Ten AD patients | ||||
Clinical study | 90 controls | Increased activity of the hippocampus, frontal, and temporal lobes of asymptomatic offspring of AD patients | fMRI | [17] |
95 asymptomatic offspring of AD patients | ||||
Clinical study | 15 controls | Increased hippocampal activity in less impaired MCI subjects compared to controls | fMRI | [8] |
15 less impaired MCI patients | Decreased hippocampal activity in more impaired MCI and mild AD subjects compared to control | |||
12 more impaired MCI patients | ||||
Ten mild AD patients | ||||
Clinical study | 19 controls | Increased activity in the posterior hippocampal, parahippocampal and fusiform regions of MCI patients vs controls | fMRI | [10] |
14 subjects with MCI | Brain activity of AD patients was not significantly different from control | |||
11 patients with mild AD | ||||
Animal models | ||||
Frontal, central, parietal, and occipital cortices of freely moving control and hAPP-J20 mice | 3–7 months non-transgenic mice (n = not specified) | hAPP-J20 mice had frequent generalized cortical epileptiform discharges, which were absent in the control | EEG | [26] |
3–7 months mice expressing hAPP | ||||
Swedish and Indiana mutations (n = 6 mice) | ||||
Neurons of L2/3 frontal cortex of live control and APP23xPS45 mice | 6–10 months control mice (n = 10 mice; 564 neurons) | Greater number of hyperactive (>4 transients/min) neurons in APPswe/PS1G384 mice | Calcium imaging | [11] |
6–10 months APPswe/PS1G384A mice (n = 20 mice; 564 neurons) | ||||
L2/3 pyramidal neurons of cortical slices | 3–4.5 months non-transgenic mice (n = 10 mice; 6 neurons) | Current injection induced action potential firing in APdE9 mice at subthreshold stimulus compared to controls | Whole-cell patch-clamp | [15] |
Frontal cortex of freely moving control and APdE9 mice | 3–4.5 months mice harboring APPswe and PSEN1dE9 mutations | 25–65% of APdE9 mice had seizures, while none of the control animals exhibited this phenotype | EEG | |
(n = 20 mice; nine neurons) | ||||
Pyramidal neurons of lateral amygdala slices of APOE3 and APOE4 mice | 1 and 7 months human APOE3/E3 knock-in mice (n = 11 mice; 23 neurons) | Reduced frequency of spontaneous excitatory postsynaptic currents in APOE4/E4 mice | Whole-cell patch-clamp | [32] |
1 and 7 months human APOE4/E4 knock-in mice (n = 12 mice; 28 neurons) | ||||
CA1 pyramidal neurons of live control and APP23xPS45 mice | 1–2 months control mice (n = 6 mice; 693 neurons) | Greater number of hyperactive (>20 transients/min) neurons in APPswe/PS1G384A mice | Calcium imaging | [28] |
1–2 months APPswe/PS1G384A mice (n = 7 mice; 818 neurons) | ||||
6–7 months control mice (n = 5 mice; 312 neurons) | ||||
6–7 months APPswe/PS1G384A mice (n = 5 mice; 349 neurons) | ||||
Neurons of CA1 hippocampal slices of APP/PS1 mice | 10–14 months control mice (n = 16 mice; 35–75 neurons) | Higher frequency of spontaneous action potential in APPswe/PS1M146V animals | Whole-cell patch-clamp | [12] |
10–14 months APPswe/PS1M146V mice (n = 16 mice; 44–69 neurons) | ||||
Cortex and hippocampus of live control and Tg2576 mice | 5wo WT mice (n = 17) | Synchronized transient spike-like events were detected in Tg2576 mice but absent in WT mice | EEG | [29] |
5wo APPswe mice (n = 9) | ||||
Neurons of L2/3 frontal cortex of live control and APP23xPS45 mice | 10–14 months control mice (n = 9 mice; 226 neurons) | Greater number of hyperactive (>4 transients/min) neurons in APPswe/PS1G384A | Calcium imaging | [27] |
10–14 months APPswe/PS1G384A (n = 10 mice; 260 neurons) | ||||
2D and 3D cell culture models | ||||
iPSC-derived neurons | iPSCs from one sporadic AD patient | Sporadic AD neurons had spontaneous Ca2+ responses and control neurons remained inactive in the absence of stimulus | Calcium imaging | [13] |
(n > 30 from three independent experiments) | iPSCs from one healthy individual | |||
iPSC-derived neurons | APOE4/4 iPSCs from one sporadic AD patient | Higher frequency of miniature excitatory postsynaptic current in APOE4/4 neurons | Whole-cell patch-clamp | [37] |
(n = 7–9 from three independent cultures) | APOE3/3 isogenic control iPSCs | |||
3D coculture of iPSC-derived neurons and astrocytes (n = >3 independent experiments) | Lentiviral-transduced human neural progenitor cells expressing both | Increased spontaneous Ca2+ transients in FAD neurons | Calcium imaging | [38] |
Swedish and London APP | ||||
mutations | ||||
Control human neural progenitor cells | ||||
2D and 3D cultures of cortical neurons | iPSCs from one healthy individual | Higher frequency of spontaneous action potential in 2D AD neurons | Whole-cell patch-clamp | [14] |
(n = 13) | iPSCs from healthy individuals edited by CRISPR/Cas9 to express | Increase in spontaneous action potential firing rate in 3D AD neurons | MEA | |
APPswe or PS1M146V mutation | ||||
iPSCs from another healthy individual | ||||
iPSCs from healthy individuals edited by TALEN to express PS1dE9 mutation |
AD Alzheimer’s disease, EEG electroencephalogram, FAD familial Alzheimer’s disease, fMRI functional magnetic resonance imaging, iPSC induced pluripotent stem cells, MCI mild cognitive impairment, MEA microelectrode array, WT wild-type.