Sangram Sisodia on Sorrento: More Fun, Less Amyloid for Transgenic Mice

COMMENT Reply by Sangram Sisodia and Orly Lazarov The cage-mates in our study were all littermates; therefore three to four animals shared a cage in our enrichment experiment. I agree that much more needs to be done to validate the model and the outcomes. ssisodi

Erik Jansson on Sorrento Secretase News: Baiting β, Awakening α

COMMENT One effective way to enhance adequate functioning of the α-secretase, which is zinc-based, may be to maintain normal zinc serum levels. Tully from the Nun Study found that normal fasting serum zinc, measured one year before death, showed moderate to stron

Hans-Gert Bernstein on Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes?

COMMENT Besides some interesting new aspects, this paper contains old wine in new wineskins. Especially the local synthesis of insulin in the brain has been shown so many times before by different researchers (Havrankova, Dorn, Bermstein, Vilanova, Raizada, Froli

Dominic Walsh on Varicose Axons: Traffic Jams Precede AD Pathology in Mice, Men

COMMENT This excellent study clearly demonstrates that axonal damage occurs long before amyloid deposition in both early stage AD and an APP mouse model. Furthermore, the authors demonstrate that reduced expression of the motor protein KCL-1 increases both the pr

Gary Arendash on Sorrento: More Fun, Less Amyloid for Transgenic Mice

COMMENT The informative paper by Lazarov and colleagues is a logical extension of our earlier study, wherein we showed that environmental enrichment to "aged" APPsw transgenic mice provides global cognitive improvement without reducing their already wel

Joanna Jankowsky on Sorrento: More Fun, Less Amyloid for Transgenic Mice

COMMENT The main point of commonality between our work on environmental enrichment and plaque deposition (Jankowsky et al., 2003) and that of Lazarov et al. is the demonstration that environment can substantially influence the level of amyloid and Aβ peptide in t

George Martin on Homing in on intracellular Abeta?

COMMENT This is a thoughtful commentary on the important paper from the UC-Irvine group, published in the same issue of Neuron, which provides evidence for an early impact of intraneural A beta upon cognition in the LaFerla triple mutant model of AD. I agree that

George Martin on Human-like rodent amyloid-beta-peptide determines Alzheimer pathology in aged wild-type Octodon degu.

COMMENT We need more reports of the neuropathology of aging members of exotic mammalian species. Here is an example that deserves some further investigation as a model of AD. These Chilean "degus" are more closely related to guinea pigs than to lab mice

George Martin on Brain glucose metabolism in the early and specific diagnosis of Alzheimer's disease. FDG-PET studies in MCI and AD.

COMMENT This is a timely and comprehensive review of almost 200 English language FDG-PET studies in MCI and AD published between 1989 and 2004. Dr. Mosconi's conclusion is optimistic: "All told, there is considerable promise that early and specific diag

Lary Walker on Visualizing Success with MRI of Amyloid Plaques in Live Mice

COMMENT Alzheimer's disease is diagnosed definitively by the presence of amyloid and tau pathology in the context of dementia. Because plaques and tangles (the canonical AD lesions) can be detected with certainty only by histological analysis, a method of vi

Jorge Parodi on Human-like rodent amyloid-beta-peptide determines Alzheimer pathology in aged wild-type Octodon degu.

COMMENT This is a new model, offering a new idea about Alzheimer disease. Maybe we can use a natural pathology to understand the disease in humans. 0 jparodi

Lars Bertram on Variation in the urokinase-plasminogen activator gene does not explain the chromosome 10 linkage signal for late onset AD.

COMMENT From the "AlzGene" team: We would like to alert AlzGene users that for SNP rs2227564 (P141L) there is potential overlap between the "Mayo" sample (Myers, 2004) and the "MCR" sample (Ertekin-Taner, 2005). However, since a) the

Lars Bertram on Elevated amyloid beta protein (Abeta42) and late onset Alzheimer's disease are associated with single nucleotide polymorphisms in the urokinase-type plasminogen activator gene.

COMMENT From the "AlzGene" team: We would like to alert AlzGene users that for SNP rs2227564 (P141L) there is potential overlap between the "Mayo" sample (Myers, 2004) and the "MCR" sample (Ertekin-Taner, 2005). However, since a) the

Bradley Hyman on Visualizing Success with MRI of Amyloid Plaques in Live Mice

COMMENT This interesting paper describes modification of a probe that crosses the blood brain barrier to become an MRI contrast agent. The exact specificity and sensitivity of the probe are still below what one would want to see in a clinical reagent, and the ima

Erik Jansson on Varicose Axons: Traffic Jams Precede AD Pathology in Mice, Men

COMMENT Aluminum could be a co-factor in the findings of Stokin and collegues. Aluminum was found to inhibit neurofilament assembly, cytoskeletal incorporation, and axonal transport by Shea et al, 1997. Deloncle et al, 2001 found that aluminum L-glutamate causes