Short summary of Alzheimer's disease

1. SANSKAR COLLEGE OF PHARMACY AND REASERCH,
NH-9, Jindal Nagar, GHAZIABAD, INDIA
ALZHEIMER: pathophysiology and treatment
Sneha pandey, Vipin Kumar, Dr. Shabnam Ain,Dr. Babita Kumar
Introduction
Although the prevalence of dementia continues to increase worldwide, incidence in the western
world might have decreased as a result of better vascular care and improved brain
health[1].Alzheimer’s disease is characterized by degenerative changes in a variety of
neurotransmitter systems. These include alterations in the function of the monoaminergic neural
systems that release glutamate, norepinephrine, and serotonin as well as a few neuropeptide-
containing systems. Alzheimer’s disease is also characterized by degenerative changes in selected
brain regions, including the temporal and parietal lobes and restricted regions within the frontal
cortex and cingulate gyrus[2].Alzheimer’s disease develops from multiple factors, such as
genetics, lifestyle and environment[3].The strongest genetic risk factor is from an allele of
APOE[4].Alzheimer’s disease is believed to occur when abnormal amounts of amyloid beta (Aβ),
accumulating extracellularly as amyloid plaques and tau proteins, or intracellularly as
neurofibrillary tangles, form in the brain, affecting neuronal functioning and connectivity,
resulting in a progressive loss of brain function[5]. There’s currently no cure for Alzheimer’s
disease. But there is medicine available that can temporarily reduce the symptoms the main
medicines are: Acetylcholinesterase (AChE) inhibitors, Memantine, Risperidone , Antidepressants
etcetc[5].
PATHOPHYSIOLOGY
Amyloid hypothesis[6]
APP cleavage -----Insoluble protein(Abeta42) accumulation- deregulate Ca homeostasis
Microglial activation Reduce iron and copper in brain senils plaques
Formation of NFTs Oxidative stress and DNA damage Neural Death

2. Mitochondrial dysfunction Alzheimer’s disease
CHOLINERGIC HYPOTHESIS ( Frist theory related to AD Pathogensis)[6]
Loss of cholinergic neuron -- Decrease acetyltransferase - Decrease Ach
Loss signal transmission
TAU HYPOTHESIS [6]
Increase Hyperphosphorylated protein formation of NFs-Affect Axonal transport  Neural death
Genetic Mechanism[7]
Mutation on three gene know as causative gene code Amyolid precursor proteins on Chromosome
21q21(APP) , Presenilin 1 on chromosome 14q24(PSENI1) and Presenilin 2 on chromosome
1q42(PSENI2). Susceptibility gene encode ApolipoproteinE on chromosome 19q13(APOE).
TREATMENT[8]
There is no cure for AD. Some drugs used to reduce symptoms these are :
Cholinesterase inhibitors( first medicine): Boost cell to cell communication , Preserve Ach.
Memantine( Namenda): Slow the progression of symptoms with moderate to severe AD.
Aduhelm(Approved in 2021[8]) :Reduce Amyolid deposits[9].
Lecaneman(Approved in 2023) :Used to treat mild AD and cognitive impairment due to AD.
Prevent Amyolid plaques clumping[8].
Antidepressants: Given if depression is suspected[8].
RESULTS
More than 6 million Americans of all ages have Alzheimer’s.An estimated 6.5 million Americans
age 65 and older are living with Alzheimer’s in 2022. Seventy-three percent are age 75 or
older.About 1 in 9 age 65 and older (10.7%) has Alzheimer’s [3].

3. CONCLUSION
Alzheimer’s disease is thought to be caused by the abnormal build-up of proteins( Amyolid and
tau) in and around brain cells. It's not known exactly what causes this process to begin. Symptoms
appear as brain cells become affected, there’s also a decrease in neurotransmitters. There is no
cure for AD but some drugs are used to reduce symptoms Aduhelm and lecaneman are the drug
used to reduce Amyolid plaques.
Reference
[1]Philip Scheltens, Kaj Blennow, Monique MB Breteler, Bart De Strooper Frontiers in Neurology
10, 1312, 2020.
[2] Gary L Wenk ,Clinical interventions in aging 2 (3), 347-359, 2007
[3]www.alz.org
[4] Long JM, Holtzman DM( October 2019) AD an update on pathobiology and treatment.
[5]www.nhs.uk
[6]www.researchgate.com
[7] Breunol P.Imbimbo, Jay Lomard, Nunzio Pomara, December 2005 Neuroimaging clinics of
North America 15(4) :727.53ix.
[8]ncbi.nlm.nih.gov
[9]my.clevelandclinic.org