ALZHEIMER’S DISEASE:PATHOPHYSIOLOGY AND TREATMENT

Presented by: Fariha Fatima

JR-1

Department of Pharmacology

INTRODUCTION:

• Alzheimer’s disease (AD) is the commonest progressive, dementing

neurodegenerative disease in elderly, which affects innumerable

people each year, and these numbers are likely to further increase as

the population ages.

• In addition to the financial burden of AD on health care system, the

disease has powerful emotional impact on caregivers and families of

those afflicted.

Aloysius ”Alois” Alzheimer

• German psychiatrist

• Described symptoms + pathology• Neuronal loss• Plaques• Tangles

Cipriani et al. (2011) Neurological Sciences, 32(2), 275-279.

1864-1913

PATHOPHYSIOLOGY:

• Alzheimer’s disease is characterized by the loss of neurons and

synapses in the cerebral cortex and certain subcortical regions.

• This loss results in gross atrophy of the affected regions , including

degeneration in the temporal lobe and parietal lobe and parts of frontal

cortex and cingulated gyrus.

• The main pathological hallmarks of Alzheimer’s disease includes:

extracellular deposition of ß-amyloid (Aß) plaques,

intraneuronal neurofibrillary tangles.

Loss of cortical cholinergic neurones in AD probably accounts for

memory impairment.

• Further research, particularly in the genetic domain, led to

identification of APP and Presenilin genes (APP, PSEN1, and

PSEN2) and mutations in these genes as cause of rare forms of

early-onset familial AD.

• On other hand, ε4 allele of apolipoprotein E gene (APOE) has been

recognized as a major risk factor for late-onset AD.

• Later, insight into the molecular pathogenesis of AD came

through many transgenic mouse models and tissue culture studies

of AD which led to the proposition of the “amyloid cascade

hypothesis”.

• However, there is growing evidence for the role of additional factors

such as oxidative stress, neuroinflammation, and mitochondrial

dysfunction in the pathogenesis of AD.

DIAGNOSIS:

• Detailed patient history

• Information from family and friends

• Laboratory tests like:

Rule out vit B12 and folate deficiency

Rule out hypothyroidism with TFT tests

Blood cell count , serum electrolyte and LFT

• Other diagnostic tests:

CT, PET or MRI scans may aid diagnosis.

• Currently, clinical diagnosis of AD is based on the National Institute of

Neurological Disorders and Stroke—Alzheimer’s Disease and Related

Disorders Association (NINCDS–ADRDA) criteria.

• As the diagnostic criteria is based on the appearance of clinical

symptoms, the time when AD pathology has progressed sufficiently

they fail to detect subjects at preclinical stage.

Therefore, there is a growing need for the development of measures

which can detect patients at an early stage.

Various biomarkers in AD can at least partly serve this purpose.

They can detect the patients with AD in their preclinical stage, monitor

the disease progression.

TREATMENT:

There is NO CURE for

Alzheimer’s disease!!!

• Improving symptomatic decline by improving cognitive function, daily activities, and behavior

• Current therapy

• Arrests the neurodegenerative molecular process

• Research needed

Primary goals of therapy are:

TARGETS OF DRUG ACTION FOR A.D.

Future of AD Research

1. Symptomatic Treatments:

- Nicotinic-receptor Agonists/Antagonists

- Serotonin-receptor Agonists/Antagonists

2. Disease-modifying Treatments:

- Inhibition of amyloid formation

- beta and gamma-secretase inhibitors

- Inhibition of abeta aggregation

- Tau phosphorylation inhibitors

The “Do-It-Yourself” Approach:

-Diet control

- Use of exercise

- Stress control

- Herbal remedies

CONCLUSION:

• Cholinergic agents initially improve and transiently maintain cognitive

abilities in patients with mild-to-moderate AD.

• Cognitive abilities worsen over time, indicating treatment does not

stop (but may delay) the progression of AD.

• New treatments that maintain cognitive ability and stop the

progression of AD are needed .