REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
TauC3 (Cleaved Asp421, Asp422)	Invitrogen	Cat# AHB0061; RRID: AB_2536237
Cleaved caspase-3 (Asp175)	Cell Signaling	Cat# 9661S; RRID: AB_2341188
Total tau K9JA	DAKO	Cat# A0024; RRID: AB_10013724
GAPDH (clone 6C5)	Millipore Sigma	Cat# MAB374; RRID: AB_2107445
Anti-Tau (3-repeat isoform RD3) clone 8E6/C11	Millipore	Cat# 05–803; RRID: AB_310013
Anti-Tau (4-repeat isoform RD4) clone 1E1/A6	Millipore	Cat# 05–804; RRID: AB_310014
Anti-Tau-1 Antibody, clone PC1C6	Millipore	Cat# MAB3420; RRID: AB_94855
Total tau Tau12	Millipore	Cat# MAB2241; RRID: AB_11211810
Anti-p62	Progen	Cat# GP62-C; RRID: AB_2687531
LC3A/B	Cell Signaling	Cat# 4108S; RRID: AB_2137703
Tau Monoclonal Antibody (Tau5)	Invitrogen	Cat# AHB0042; RRID: AB_2536235
Phospho-Tau (Ser202, Thr205) Monoclonal Antibody (AT8)	Invitrogen	Cat# MN1020; RRID: AB_223647
VGlut1	Synaptic Systems	Cat# 135304; RRID: AB_887878
VGAT	Synaptic Systems	Cat# 131008; RRID: AB_2800534
Anti-PSD95	Abcam	Cat# Ab18258; RRID: AB_444362
Anti-PSD-95 Antibody (K28/43)	NeuroMab/Antibodies Inc	Cat# 75–028; RRID: AB_2292909
Rabbit anti-GFAP	DAKO	Cat# Z0334; RRID: AB_10013382
Homer1	Synaptic Systems	Cat# 160002; RRID: AB_2120990
Anti-GluA1/GluR1 (N355/1)	NeuroMab/Antibodies Inc	Cat# 75–327; RRID: AB_2315840
Anti-Glutamate Receptor1 Ab, phosphoSer845	Millipore	Cat# AB5849; RRID: AB_92079
Goat anti-Mouse IgG (H+L) Secondary Antibody, HRP	Invitrogen	32430
Goat anti-Rabbit IgG (H+L) Secondary Antibody, HRP	Invitrogen	32460
Goat anti-Mouse IgG (H+L)- Highly crossed absorbed (HA) Secondary Antibody, Alexa Fluor™ 488	Invitrogen	A32723
Goat anti-Mouse IgG (H+L) Secondary Antibody, Alexa Fluor™ 488	Invitrogen	A11001
Donkey anti-Mouse IgG (H+L) Secondary Antibody, Alexa Fluor™ 488	Life technologies	A21202
Goat anti-Guinea pig IgG (H+L) Secondary Antibody, Alexa Fluor™ 568	Invitrogen	A11075
Donkey anti-Mouse IgG (H+L) Secondary Antibody, Alexa Fluor™ 568	Invitrogen	A10037
Donkey anti-Rabbit IgG (H+L) Secondary Antibody, Alexa Fluor™ 594	Invitrogen	A21207
Goat anti-Rabbit IgG (H+L)-HA Secondary Antibody, Alexa Fluor™ 594	Invitrogen	A32740
Goat anti-Rabbit IgG (H+L)-HA Secondary Antibody, Alexa Fluor™ 647	Invitrogen	A32733
Donkey anti-Rabbit IgG (H+L) Secondary Antibody, Alexa Fluor™ 647	Invitrogen	A31573
Biological samples
Control 1-5 cortex (IB)	University of Pennsylvania (CNDR) Biorepository	Case 1-5
Alzheimer’s disease 1-6 cortex (IB)	University of Pennsylvania (CNDR) Biorepository	Case 6-11
Alzheimer’s disease 1 hippocampus (IHC)	UNC Biorepository (TPL)	Case 12
Chemicals, peptides, and recombinant proteins
MG132	Sigma	M7449
Bortezomib	Millipore	5.04314.0001
Epoxomicin	Sigma	E3652
Lactacystin	Enzo Life Sciences	BML-PI104-0200
Staurosporine	Enzo Life Sciences	ALX-380-014-M001
Chloroquine diphosphate (CQ)	Sigma	6628
3-methyladenine (3-MA)	Sigma	M9281
Rotenone	Sigma	R8875
Bicuculline	Tocris	0109
Tetrodotoxin citrate	Tocris	1069
DAPI	ThermoFisher	D1306
Thioflavin S	Sigma	T1892
Critical commercial assays
CytoTox 96® Non-Radioactive Cytotoxicity Assay (LDH)	Promega	G1780
CellTiter 96® Non-Radioactive Cell Proliferation Assay (MTT)	Promega	G4000
Experimental models: Cell lines
HEK293A	ThermoFisher	R70507
Experimental models: Organisms/strains
C57Bl/6	Charles River	Strain Code: 027
CD1	Charles River	Strain Code: 022
Tau knockout (KO)	Jackson Laboratory	Strain Code: 7251
Caspase-3 knockout (KO)	Jackson Laboratory	Strain Code: 006233
Oligonucleotides
Tau KO-F 5′-cattgctgccaagttcaccttag	This paper	N/A
Tau KO-R 5′-tgttttgccaagttctaattccatcaga	This paper	N/A
Tau KO reporter 1 5′-ctagaggatccccgggtacc	This paper	N/A
Caspase-3 common-R 5′-gcgagtgagaatgtgcataaattc	This paper	N/A
Caspase-3 WT-F 5′-gggaaaccaacagtagtcagtcct	This paper	N/A
Caspase-3 KO-F 5′-tgctaaagcgcatgctccagactg	This paper	N/A
Tau-F (33-mer) 5′-ccgaccggtgccaccatggctgagccccgccag	This paper	N/A
Tau-R (31-mer) 5′-cgcgtcgactcacaaaccctgcttggccagg	This paper	N/A
pUltra tau 1-421-R (33-mer) 5′-cgcgtcgactcagtctaccatgtcgatgctgcc	This paper	N/A
D421A-F (26-mer) 5′-gacatggtagcctcgccccagctcgc	This paper	N/A
D421A-R (21-mer) 5′-gatgctgccggtggaggagac	This paper	N/A
pTX181- control GFP Agel-BsrG1, filled in	This paper	N/A
Recombinant DNA
pTX713 pcDNA5/TO tau T34 (1N4R)	Trzeciakiewicz et al.98	N/A
pTX714 pcDNA5/TO tau T37 (1N3R)	Trzeciakiewicz et al.98	N/A
pTX715 pcDNA5/TO tau T39 (2N3R)	Trzeciakiewicz et al.98	N/A
pTX716 pcDNA5/TO tau T43 (0N4R)	Trzeciakiewicz et al.98	N/A
pTX717 pcDNA5/TO tau T44 (0N3R)	Trzeciakiewicz et al.98	N/A
pTX096 pcDNA5/TO tau T40 (2N4R)	Trzeciakiewicz et al.98	N/A
pTX407 pcDNA5/TO tau T40 ΔR1	Trzeciakiewicz et al.98	N/A
pTX408 pcDNA5/TO tau T40 ΔR2	Trzeciakiewicz et al.98	N/A
pTX409 pcDNA5/TO tau T40 ΔR3	Trzeciakiewicz et al.98	N/A
pTX410 pcDNA5/TO tau T40 ΔR4	Trzeciakiewicz et al.98	N/A
pTX411 pcDNA5/TO tau T40 ΔR1-4	Trzeciakiewicz et al.98	N/A
Software and algorithms
Prism Version 9	GraphPad Software	https://www.graphpad.com/features
ImageJ	Schneider et al.99	https://imagej.nih.gov/ij/
Zen	Zeiss	https://www.zeiss.com/microscopy/en/products/software/zeiss-zen.html
Python (Anaconda 64-bit v3.8.8) code and standard libraries such as numPy, NetworkX, and SciPy.	Python	https://www.python.org
Other
Trypsin	Promega	25200-056
Dulbecco’s Modified Eagle Media (DMEM)	Gibco	31-053-028
Fetal bovine serum (FBS)	Sigma	F2442
L-glutamine	Gibco	25030-081
FuGENE 6 Transfection Reagent	Promega	E2691
Protein A/G PLUS-Agarose beads	Santa Cruz	sc-2003
Penicillin/Streptomycin	Thermo Scientific	15140-122
BrainPhys Neuronal Medium	StemCell Technologies	05790
GlutaMAX Supplement	Gibco	35050061
B-27 Supplement	Gibco	2450384