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Aging in Dogs
Elizabeth Head, Ph.D.
Sanders-Brown Center on Aging
University of Kentucky
Lexington, KY
1. Ab sequence is
identical
2. APP sequence virtually
identical (only 21/770
aa differ on the longest
isoform = 98.4%
homo...
Ab biomarkers in dogs
Head et al., 2010.
Similar to observations in AD –
overall lower levels of CSF Ab 1-42
Cerebrovascular Pathology
in Aging Dogs
• Cerebral amyloid angiopathy
• Typically associated with shorter more
soluble Ab1...
Neurobiological Changes in Aging Dogs
Cognition declines with age
Young Old
TotalNumberDCX/BrdU+Neurons
0
500
1000
1500
20...
Other thoughts
What dogs do not show:
• Full blown tangles – some
evidence for tau
phosphorylation – sequence
differences ...
Elizabeth Head Alzforum Webinar - Dec 7, 2016
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Elizabeth Head Alzforum Webinar - Dec 7, 2016

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Presentation made at the Alzforum's live webinar of December 5, 2016, titled "Is Alzheimer’s Disease a Uniquely Human Disorder?" - review additional information and recording at www.alzforum.org/

Published in: Health & Medicine

Elizabeth Head Alzforum Webinar - Dec 7, 2016

  1. 1. Aging in Dogs Elizabeth Head, Ph.D. Sanders-Brown Center on Aging University of Kentucky Lexington, KY
  2. 2. 1. Ab sequence is identical 2. APP sequence virtually identical (only 21/770 aa differ on the longest isoform = 98.4% homologous) 3. Canine genome published: http://www.ensembl.or g/Canis_familiaris/ 4. Age-dependent cortical accumulation 5. Correlated with cognition Ab Pathology First noted plaques in the brains of aged dogs in 1956 by Braunmuhl (silver staining) Wisniewski et al first suggested the dog as a model for amyloidogenesis in 1970 Parietal Cortex 2 4 6 8 10 12 14 16 18 20 AmyloidLoad(%) 0 5 10 15 20 25 Occipital Cortex 2 4 6 8 10 12 14 16 18 20 0 5 10 15 20 25 Prefrontal Cortex Chronological Age (years) 2 4 6 8 10 12 14 16 18 20 0 5 10 15 20 25 Entorhinal Cortex 2 4 6 8 10 12 14 16 18 20 0 5 10 15 20 25
  3. 3. Ab biomarkers in dogs Head et al., 2010. Similar to observations in AD – overall lower levels of CSF Ab 1-42
  4. 4. Cerebrovascular Pathology in Aging Dogs • Cerebral amyloid angiopathy • Typically associated with shorter more soluble Ab1-40 • May affect vasodilation and constriction function of blood vessels • Microhemorrhages increase with age • Need for more imaging studies in dogs (e.g. ASL, T2*, FLAIR)
  5. 5. Neurobiological Changes in Aging Dogs Cognition declines with age Young Old TotalNumberDCX/BrdU+Neurons 0 500 1000 1500 2000 2500 Reduced neurogenesisReduced neuron numbers in hilus Parietal Synaptophysin Age 0 2 4 6 8 10 12 14 16 18 SynaptophysinAdjustedOD(raw/actin) 0 50 100 150 200 250 Synapse protein loss with age BDNFmRNACopyNumber 0 2000 4000 6000 8000 10000 12000 Young Aged Loss of growth factors Age Effects on Mitochondrial Generation of ROS Time (minutes) 4 6 8 10 12 14 16 ROSGeneration 0 200 400 600 800 1000 1200 Young Animals Aged Animals p<.002 p<.002 p<.004 Mitochondrial dysfunction
  6. 6. Other thoughts What dogs do not show: • Full blown tangles – some evidence for tau phosphorylation – sequence differences – is there such a thing as canine tangles? • Significant glial responses to Ab– is this because Ab is primarily diffuse (although fibrillar at ultrastructural level) • Inflammation appears to not be as pronounced as in human brain although needs more systematic study What dogs may be useful for: • Environmental contributions to brain aging/neuropathology – e.g. pet dogs vs laboratory dogs?

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