Neuropathology consistent with AD.

Increased Aβ42/Aβ40 and Aβ42/Aβ38; unchanged Aβ38/Aβ40 and Aβ43/Aβ40 in iPSC-derived neurons, suggesting inefficient carboxypeptidase activity.Variable protein levels, consistent with altered protein stability. Also, disrupted lysosome function and autophagy seemingly due to accumulation of β-C-terminal APP fragments.

Neuropathology consistent with AD in 3 cases, but more involvement of central grey areas, no vascular lesions, and very mild amyloid angiopathy.

Increased Aβ42/Aβ40 and Aβ42/Aβ38; unchanged Aβ38/Aβ40 and Aβ43/Aβ40 in iPSC-derived neurons, suggesting inefficient carboxypeptidase activity. Variability in mutant protein levels, consistent with altered protein stability. Also, disrupted lysosome function and autophagy seemingly due to accumulation of β-C-terminal APP fragments. 

Unknown, but carriers of a different nucleotide mutation resulting in the same amino acid substitution had neuropathology consistent with AD.

Increased Aβ42/Aβ40 and Aβ42/Aβ38; unchanged Aβ38/Aβ40 and Aβ43/Aβ40 in iPSC-derived neurons, suggesting inefficient carboxypeptidase activity. High degree of variablilty in mutant protein levels, consistent with altered protein stability. Also, disrupted lysosome function and autophagy seemingly due to accumulation of β-C-terminal APP fragments.

Neuropathology consistent with AD in multiple affected mutation carriers. Pick bodies and Lewy body pathology, as assessed by α-synuclein staining, have been noted in some cases.

Increased Aβ42/Aβ total ratio, Aβ42/Aβ40 ratio, and Aβ42. Disrupted calcium dynamics and mitochondrial permeability.

Neuropathology consistent with AD. In one case, Lewy body pathology in the amygdala, cingulate gyrus, and substantia nigra. 

Increased Aβ42, Aβ42/Aβ total, Aβ42/Aβ40 in cells and in vitro assays. Impaired calcium dynamics and mitochondrial permeability.

Variable: Neuropathology consistent with AD in some cases, but also, in at least one case, mixed pathology including frequent Aβ deposits, tangles, and Pick bodies.

Increased Aβ42/Aβ40 ratio; increased Aβ42 and Aβ43; lowered wild-type PSEN1 gene expression. Disrupted endosomes via accumulation of APP β-CTF. Disrupted calcium channels, triggered cascade resulting in altered axonal transport, damage/loss of neurites. Increased calcineurin activity, impaired trafficking of glutamate AMPA receptors. Disrupted mitochondrial function, altered trophic factor function, and cerebral blood flow.