DS

AD

Alzheimers Disease
and
Down Syndrome
Two Sides of the
Same Coin
Huntington Potter, Ph.D.
Professor and Director of
Alzheimers Disease Programs
Department of Neurology and
Linda Crnic Institute for Down

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of
Neurology

First Report of Alzheimers Disease

I have lost myself

DS

Alois Alzheimer, 1907

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

BRAIN PATHOLOGY IN ALZHEIMERS DISEASE

Normal Brain
Alzheimers Brain

Plaques and tangles

Glial Inflammation

e glia showed numerous filaments and fatty vacuoles

Department of Neurology
Department of

John Langdon Down, 1866

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

Discovery of Trisomy 21 in Down Syndrome

Jrme Lejeune, Marthe

Gautier, 1958

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

The Down Syndrome and

Alzheimers Disease Connection

Alzheimers Disease
10% of people over
>5 million patients
~$172 billion annual
age 65
40-50% of people over
cost
Down Syndrome
age 85
~400,000 patients
1/691 live births
~$19 billion annual
100 % acquire
cost
features of AD

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

BRAIN PATHOLOGY IN ALZHEIMERS DISEASE

Normal Brain
Alzheimers Brain
Plaques and tangles

George Glenner and Caine Wong 1984

DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLM
VGGVVIA
A Peptide

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

The Amyloid Precursor Protein Gene Is Encoded on Chromosome 21

21

APP
The Swedish Alzheimers Disease Family
Inherits a Mutant APP Gene

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

Mice With Mutant APP Gene

Accumulate Amyloid Deposits

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

THE AMYLOID CASCADE IN AD and DS

NsAPP

Amyloid Precursor Protein

A

sAPP

-secretase
secretase
soluble A A
A protofibrils A

-C
P3
-secretase

A A

A deposition in plaques

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

Inflammatory Genes Ap
and/or ACT are Essenti
Amyloid Formation

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

RADIAL ARM WATER MAZE START

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

RADIAL ARM WATER MAZE FINISH LINE

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

A RECRIPROCAL ADDS CONNECTION

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

COUNTING CHROMOSOMES

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

Trisomy 21 In Alzheimers Disease

*
*

**

**

Skin Cells

Nerve Cells

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

DISEASES WITH CELL CYCLE DEFECTS AND

TRISOMY 21 MOSAICISM

ALZHEIMERS DISEASE (FAMILIAL AND SPORADIC)

FRONTOTEMPORAL LOBAR DEGENERATION (FAMILIAL AND SPORADIC

NIEMANN PICK C1
HUNTINGTONS DISEASE

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

Marked decline in glucose

uptake in AD and DS brain

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

PROMISING TRIALS FOR ALZHEIMERS OR DOWN SYNDROME

1. Biogen antibody

2. BACE inhibitor

3. Leukine

4. Direct Current Brain Stimulation

5. Direct Radio Frequency Stimulation

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of

APPRECIATION
Scientists: Antoneta Granic, PhD
Tim Boyd, PhD
Julbert Caneus
Michelle Norden
Jaya Padmanabhan, PhD
Jiashin Wu, PhD
Sergiy Borysov, PhD
Csilla Ari, PhD
Funding:

Linda Crnic Institute for Down Syndrome

Global Down Syndrome Foundation
Sie Center for Down Syndrome @ Childrens Hospital Colorado
UC Denver COM; Dept. Neurology
National Institute on Aging
National Institute on Neurological Diseases and Stroke
Dana Foundation
Colorado Translational Research Imaging Center
Bruce and Marcy Benson

DS

AD

ROCKY MOUNTAIN
ALZHEIMERS DISEASE CENT
Department of Neurology
Department of