Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease

A method for screening for an agent which ameliorates symptoms of Alzheimer's disease, said method comprising:

• comparing performance on memory and learning tests of a first transgenic mouse contacted with said agent with that of a second transgenic mouse not contacted with said agent, wherein the genome of said first and said second transgenic mice comprise an amyloid precursor protein transgene comprising regulatory sequences from a prion gene promoter operatively linked to a coding sequence selected from the group consisting of APP695.WT, APP695.SWE and APP695.TRI, wherein neurological expression of said transgene produces impaired performance on said memory learning tests and abnormal neuropathology in a cortico-limbic region of said mouse's brain, wherein said impaired performance and said abnormal neuropathology are in comparison with control mice, whereby an agent which ameliorates said symptoms is identified by superior performance of said first transgenic mouse in comparison with said second transgenic mouse on said memory and learning tests.

A method for screening for an agent useful for treating Alzheimer's disease, said method comprising:

• comparing performance on memory and learning tests of a first transgenic mouse contacted with said agent with that of a second transgenic mouse not contacted with said agent, wherein the genome of said first and said second transgenic mice comprise an amyloid precursor protein transgene comprising regulatory sequences from a prion gene promoter operatively linked to a coding sequence selected from the group consisting of APP695.WT, APP695.SWE and APP695.TRI, wherein neurological expression of said transgene produces impaired performance on said memory and learning tests and abnormal neuropathology in a cortico-limbic region of said mouse's brain, wherein said impaired performance and said abnormal neuropathology are compared with control mice;
• and
• comparing neuropathology in a cortico-limbic region of the brain of said first and said second transgenic mice when said first transgenic mouse exhibits superior performance on said memory and learning tests compared with said second transgenic mouse, whereby an agent which is useful for treating Alzheimer's disease is identified by a decrease in neuropathologic findings in said first transgenic mouse in comparison with said second transgenic mouse.

A method for screening for an agent useful for treating Alzheimer's disease, said method comprising:

• comparing performance on memory and learning tests of a first transgenic mouse contacted with said agent with that of a second transgenic mouse not contacted with said agent, wherein the genome of said first and said second transgenic mice comprise an amyloid precursor protein transgene comprising regulatory sequences from a prion gene promoter operatively linked to a coding sequence selected from the group consisting of APP695.WT, APP695.SWE and APP695.TRI, wherein neurological expression of said transgene produces impaired performance on said memory and learning tests and abnormal neuropathology in a cortico-limbic region of said mousers brain, wherein said impaired performance and abnormal neuropathology are in comparison with control mice;
• and
• comparing age of death of said first and said second transgenic mice when said first transgenic mouse exhibits superior performance on said memory and learning tests in comparison with said second transgenic mouse, whereby an agent which is useful for treating Alzheimer's disease is identified by a greater age at death of said first transgenic mouse in comparison with said second transgenic mouse.

A method for screening for an agent which ameliorates symptoms of Alzheimer's disease, said method comprising:

• comparing exploratory behavior or locomotor behavior of a first transgenic mouse contacted with said agent with that of a second transgenic mouse not contacted with said agent, wherein the genome of said first and said second transgenic mice comprise an amyloid precursor protein transgene comprising regulatory sequences from a prion gene promoter operatively linked to a coding sequence selected from the group consisting of APP695.WT, APP695.SWE and APP695.TRI, wherein neurological expression of said transgene produces impaired performance on said exploratory and locomotor behavior and abnormal neuropathology in a cortico-limbic region of said mouse's brain, wherein said impaired performance and abnormal neuropathology are compared with control mice, whereby an agent which ameliorates said symptoms is identified by less impaired exploratory or locomotor behavior in said first transgenic mouse in comparison with said second transgenic mouse.

A transgenic mouse with progressive neurological disease whose genome comprises:

• an amyloid precursor protein transgene comprising regulatory sequences from a prion gene promoter operatively linked to an amyloid precursor protein coding sequence having the Swedish mutation, wherein neurological expression of said transgene produces an age-dependent decline in performance of said mouse in memory and learning tests and produces amyloid plaques that are detectable by Congo red staining in the brain of said mouse, wherein said age-dependent decline in performance and said amyloid plaques are in comparison with control mice.