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LRRK2 R1441C KI Mouse

RESEARCH MODELS Overview This knock-in (KI) mouse model was generated by introducing a R1441C missense mutation into the GTPase domain at exon 31 of the mouse Lrrk2 (leucine-rich repeat kinase 2) gene (Tong et al., 2009). As such, this mutation is expressed through the c

PSEN1 A434V

MUTATIONS PSEN1 73685894 GRCh37/hg19 C T Exon 12 Coding Unknown, but predicted deleterious (PHRED-scaled CADD score = 28.7) A434V Alzheimer's Disease: Not ClassifiedAlzheimer's Disease, Posterior Cortical Atrophy This variant was identified in a 52-year-o

MAPT 10IVS+16 C>T

RESEARCH MODELS Summary MAPT 10IVS+16 C>T mice are among a series of models developed by Michael Koob and colleagues at the University of Minnesota, collectively referred to as Gene Replacement – Alzheimer’s Disease (GR-AD) mice. In GR-AD mice, “genes of interest are

MAPT(H1.0*)P301L-GR

RESEARCH MODELS Summary MAPT(H1.0)-GR mice are among a series of models developed by Michael Koob and colleagues at the University of Minnesota, collectively referred to as Gene Replacement – Alzheimer’s Disease (GR-AD) mice. In GR-AD mice, “genes of interest are precise

PSEN2 I100I

MUTATIONS PSEN2 227071564 GRCh37/hg19 rs200801915 C T Exon 5 Coding Unknown, but predicted benign in silico (PHRED-scaled CADD score = 6.52). Unknown. I100I Alzheimer's Disease: Likely BenignLate-onset This variant was reported in a preprint that analyzed data

ACP-204

THERAPEUTICS Acadia Pharmaceuticals Small Molecule Other Neurotransmitters No Phase 1 trials are registered. In investor presentations, Acadia claims that in Phase 1, ACP-204 caused no QT wave prolongation, was able to be dosed to twice the levels of Nuplazid, and rea

PSEN1 I427V

MUTATIONS PSEN1 73685872 GRCh37/hg19 rs1398951357 A G Exon 12 Coding Unknown, but predicted in silico to be damaging (PHRED-scaled CADD score = 20.3). Unknown. I427V Alzheimer's Disease: Uncertain SignificanceAlzheimer's Disease This variant was reported

PSEN1 L226V

MUTATIONS PSEN1 73659479 GRCh37/hg19 C G Exon 7 Coding Unknown, but in silico algorithm predicted a damaging effect (PHRED-scaled CADD = 28). Unknown, but imaging in one case showed a posterior gradient of atrophy including the hippocampus; white matter alterations

PSEN1 R220Q

MUTATIONS PSEN1 73659462 GRCh37/hg19 rs763831389 G A Exon 7 Coding Unknown, but in silico algorithms predicted a damaging effect (PHRED-scaled CADD = 22.9). Unknown. R220Q Alzheimer's Disease: Uncertain SignificanceAlzheimer's Disease This variant was rep

MAPT IVS9-7A> T

MUTATIONS MAPT 44087669 GRCh37/hg19 A T Intron 9 Non-Coding Alters the splice site resulting in more frequent inclusion of exon 10 into mRNA transcripts. Neuronal loss, gliosis, and accumulation of 4R tau in multiple brain areas including the temporal lobe, amygdal

PSEN2 R435Q

MUTATIONS PSEN2 227083237 GRCh37/hg19 rs201922151 G A Exon 13 Coding Unknown, but in silico algorithms predict damaging (PHRED-scaled CADD = 22.1). Unknown. R435Q Alzheimer's Disease: Uncertain SignificanceAlzheimer's Disease This variant was reported in

Focused Ultrasound – Blood-Brain Barrier

THERAPEUTICS FUS-BBB MRgFUS MRI-Guided Focused Ultrasound FUS+MB Procedural Intervention Amyloid-Related Other In 2016-2017, a feasibility trial in Ontario enrolled five people with mild Alzheimer’s disease for two rounds of focused ultrasound, spaced one month apart

NYX-458

THERAPEUTICS Aptinyx Inc. Small Molecule Other Neurotransmitters In November 2019, Aptinyx began a Phase 2 study in people with Parkinson’s disease or Lewy body disease with mild cognitive impairment or mild dementia. The 99 participants took 30 mg NYX-458 or placebo

NA-831

THERAPEUTICS Biomed Industries NeuroActiva™ Inc. Traneurocin Small Molecule Cholinergic System In Phase 1, 32 healthy volunteers in four cohorts received multiple doses of NA-831 ranging from 5 to 50 mg daily over one week. At AAIC 2018, the compound was shown having

NTRX-07

THERAPEUTICS 1-[(3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl)carbonyl]piperidine NeuroTherapia, Inc. MDA7 Small Molecule Inflammation Other From October 2019 to December 2020, NeuroTherapia conducted a Phase 1, single-ascending-dose study in 48 healthy volunteers.

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