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Figure 35.6 Beta-amyloid immunostaining in the hippocampus of a 5-year-old dog (A) and a 12-year-old dog (B) and in the temporal cortex of a 12 year-old-dog (C). Higher magnification in the 12-year-old (D) illustrates the presence of intact neurons (arrow) in the diffuse plaques. Bar in D is 20 ^m. See the color plate section.

Figure 35.6 Beta-amyloid immunostaining in the hippocampus of a 5-year-old dog (A) and a 12-year-old dog (B) and in the temporal cortex of a 12 year-old-dog (C). Higher magnification in the 12-year-old (D) illustrates the presence of intact neurons (arrow) in the diffuse plaques. Bar in D is 20 ^m. See the color plate section.

of the hallmarks of Alzheimer's disease, but the aged dog is particularly well-suited for studying early stages of beta-amyloid deposition in the aging brain. Plaque morphology in the dog is generally diffuse and cloudlike (Figure 35.6) and deposits are thioflavine-S negative, suggesting a lack of ^-pleated sheets formation (Satou et al., 1997).

In addition, dogs accumulate the longer, more toxic and less soluble form of A^1-42 prior to the shorter more soluble A^1-40 type, consistent with human brain aging (Cummings et al., 1996). Beta-amyloid builds up initially in and around neurons and is present within apical and basal dendrites. Furthermore, beta-amyloid is deposited uniformly in select synaptic terminal fields, such as the terminal zone of the perforant pathway, that show a predilection for extensive plaque formation in Alzheimer's disease.

The regional pattern of beta-amyloid deposition in the dog parallels human brain aging. In the dog, the earliest and most consistent distribution of beta-amyloid plaques occurs in the prefrontal cortex beginning around 8 years of age (Head et al., 1998). Early prefrontal beta-amyloid deposition is also common in nondemented (Bussiere et al., 2002) and preclinical Alzheimer's disease subjects (Yamaguchi et al., 2001). By 14 years of age, beta-amyloid deposition progresses to the entorhinal and parietal regions of the canine cerebral cortex equally, leaving the cerebellum relatively unaffected. Further, our studies reveal a strong correlation between regional beta-amyloid deposition and cognitive decline in aging dogs (Head et al., 1998; Tapp et al., 2004a).

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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