Brain & Nervous System Alzheimer's The Effects of Alzheimer's on the Brain By Christine Kennard Christine Kennard Christine Kennard is a psychiatric nurse practicing in the United Kingdom and co-author of "Alzheimer's Disease: An A-Z For New Caregivers." Learn about our editorial process Updated on February 26, 2022 Medically reviewed by Nicholas R. Metrus, MD Medically reviewed by Nicholas R. Metrus, MD LinkedIn Nicholas R. Metrus, MD, is a board-certified neurologist and neuro-oncologist. He currently serves at the Glasser Brain Tumor Center in Summit, New Jersey. Learn about our Medical Expert Board Fact checked by Heather Mercer Print The brain of someone with Alzheimer's disease is very different from that of a normal brain. Hallmark differences in plaques and tangles, as well as the cerebral cortex, account for some of these key distinctions. Understanding how the anatomy of the Alzheimer's brain differs from a normal brain gives us insight. It can help us cope better with the changes that happen to our loved ones resulting from this debilitating disease. This article discusses the role of plaques and tangles in an Alzheimer's brain and other critical differences. PASIEKA / Getty Images In an Alzheimer's brain, the cerebral cortex atrophies. That means that this area of the brain shrinks and this shrinkage is dramatically different from the cerebral cortex of a normal brain. The cerebral cortex is the outer surface of the brain. It is responsible for all intellectual functioning. There are two major changes that can be observed in the brain using magnetic resonance imaging (MRI): The amount of brain substance in the folds of the brain (the gyri) is decreasedThe spaces in the folds of the brain (the sulci) are grossly enlarged. Microscopically there are a number of changes in the brain too. These can only be viewed histologically with tissue samples taken at autopsy. At the microscopic level, the two hallmark findings in the Alzheimer's brain are amyloid plaques and neurofibrillary tangles. Amyloid plaques are found outside the neurons, neurofibrillary tangles are found inside the neurons. Neurons are the nerve cells within the brain. These plaques and tangles are also found in the brains of people without Alzheimer's. It is the density and location of them that is significant in Alzheimer's disease. These plaques and tangles cause death and shrinkage of neurons, and cause the brain to atrophy. The Role of Amyloid Plaques Amyloid plaques are mostly made up of a protein called B-amyloid protein which is itself part of a much larger protein called APP (amyloid precursor protein). These are amino acids. We do not know what APP does. But we do know that APP is made in the cell, transported to the cell membrane and later broken down. Two major pathways are involved in breakdown of APP (amyloid precursor protein). One pathway is normal and causes no problem. The second results in the changes seen in Alzheimer's and in some of the other dementias. Pathway Breakdown Leading to Alzheimer's Damage In the second breakdown pathway APP is split by enzymes β -secretase (β=beta) then γ-secretase (γ=gamma). Some of the fragments (called peptides) that result stick together and form a short chain called an oligomer. Oligomers are also known as ADDL, amyloid-beta derived diffusible ligands. Oligomers of amyloid beta 42 type (Aβ42) have been shown to be highly toxic. Aβ42 produces tiny fibers, or fibrils, and when they stick together they form an amyloid plaque that collects between neurons, causing dysfunction of cell to cell communication at the synapse. The Role of Neurofibrillary Tangles The second major finding in the Alzheimer's brain is neurofibrillary tangles. These tangles are composed of Tau proteins, which play a crucial role in the normal structure and function of the neuron. In people with Alzheimer's disease, the formally straight Tau proteins have mutated, due to overactive enzymes, resulting in twisted strands that aggregate together and become tangles. These tangles acculumulate inside the neuron, disrupt cell activity (movement of nutrients and essential supplies), and result in the death of the neuron. Alzheimer's Brain Summary The role of amyloid plaques and neurofibrillary tangles on the functioning of the brain is by no means fully understood. Most people with Alzheimer's disease show evidence of both plaques and tangles, but a small number of people with Alzheimer's only have plaques and some have only neurofibrillary tangles. People with plaque only Alzheimer's show a slower rate of deterioration during their lives. Neurofibrillary tangles are also a feature of a different degenerative brain disease called frontotemporal dementia. Research into Alzheimer's disease is finding out more and more about the anatomy and physiology of the brain. As we understand more about the role of plaques and tangles observed in the Alzheimer's brain the closer we get to a significant breakthrough and a cure for Alzheimer's disease. 6 Sources Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. Dash P, Villemarette-Pittman N. Alzheimer’s Disease. Springer Publishing Company; 2005. Cai K, Xu H, Guan H, et al. Identification of early-stage Alzheimer’s disease using sulcal morphology and other common neuroimaging indices. Ginsberg SD, ed. PLoS ONE. 2017;12(1). doi:10.1371/journal.pone.0170875 Furcila D, Domínguez-Álvaro M, DeFelipe J, Alonso-Nanclares L. Subregional density of neurons, neurofibrillary tangles and amyloid plaques in the hippocampus of patients with Alzheimer’s disease. Front Neuroanat. 2019;13:99. doi:10.3389/fnana.2019.00099 National Institute of Aging. What happens to the brain in Alzheimer's disease? Mandelkow EM, Mandelkow E. Biochemistry and cell biology of Tau protein in neurofibrillary degeneration. Cold Spring Harbor Perspectives in Medicine. 2012;2(7). doi:10.1101/cshperspect.a006247 Alheimer's Association. Inside the brain: A tour of how the mind works. Additional Reading Alzheimer's Association Alzheimers.gov National Institute of Aging: Alzheimer’s and related Dementias Education and Referral (ADEAR) Center Dash P, Villemarette-Pittman N. Alzheimer’s Disease. Springer Publishing Company; 2005. By Christine Kennard Christine Kennard is a psychiatric nurse practicing in the United Kingdom and co-author of "Alzheimer's Disease: An A-Z For New Caregivers." See Our Editorial Process Meet Our Medical Expert Board Share Feedback Was this page helpful? Thanks for your feedback! What is your feedback? Other Helpful Report an Error Submit